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NCT03345485 · REGISTRY CONDITION SEARCH

Study of the Safety, Pharmacokinetics and Efficacy of Tinostamustine in Patients With Advanced Solid Tumors.

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2024-10-21

Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor designed to improve drug access to deoxyribonucleic acid (DNA) strands, induce DNA damage and counteract its repair in cancer cells. The main purpose of this study is to assess the safety, tolerability and efficacy of Tinostamustine in subjects with advanced solid tumours. Subjects will be given Tinostamustine via intravenous infusion on Days 1 and 15 of a 4-week cycle, the dose and infusion time will vary depending on the phase of the study.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1

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outcome · POSTED

Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2

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outcome · POSTED

Highest Change From Baseline in QTcF in Sub-studies

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outcome · POSTED

Treatment-related Adverse Events on Phase 2 and Sub Studies

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outcome · POSTED

Progression Free Survival (PFS) Time for Phase 2 and Sub Studies

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outcome · POSTED

Overall Survival (OS) Time for Phase 2 and Sub Studies

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outcome · POSTED

Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies

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outcome · POSTED

Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies

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outcome · POSTED

Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies.

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outcome · POSTED

Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies

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outcome · POSTED

Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies.

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outcome · POSTED

Summary of Tmax in in Phase 2 and Sub Studies.

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outcome · POSTED

Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies

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outcome · POSTED

Summary of Half-life of Tinostamustine in Phase 2 and Substudies.

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion and exclusion criteria were reviewed for each potential patient during Screening. All eligible patients were treated with Tinostamustine employing sequential enrollment (i.e. as they qualify for participation). In the first phase of the trial (Phase 1), the dose received for each eligible patient was dependent on the requirements of the dose escalation scheme at the time the patient was enrolled. In the second phase of the trial (Phase 2), all patients were treated with the Tinostamustine at 80 mg/m2 administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle. General Inclusion Criteria for Phase 1 and Phase 2 portions of Study: 1. Patient willing and able to sign the informed consent. 2. Patients age ≥18 years at signing the informed consent. 3. Life expectancy \> 3 months. 4. Histologically confirmed diagnosis of advanced or metastatic solid tumors, disease should have progressed following at least one line of therapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient. 5. Patients with secondary metastasis to the central nervous system (CNS) are eligible if they have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to trial day 1 and they meet all of the following criteria: 1. Residual neurological symptoms ≤Grade 1. 2. No glucocorticoids requirement or patients may be receiving low doses of glucocorticoids providing the dose has been stable for at least 2 weeks prior to starting the trial medication. 3. Follow-up imaging studies show no progression of treated lesions and no new lesions. 6. Evaluable disease; measurable on imaging as assessed by RECIST version 1.1. 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 8. Absolute neutrophil count (ANC) (polymorphonuclear cells \[PMN\] plus bands) \>1,000/ μL. 9. Platelets ≥100,000 μL. Platelet transfusions within the 14 days before Day 1 of Cycle 1 is prohibited. 10. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 3 upper limit of normal (ULN). In cases with liver involvement ALT/ AST ≤ 5× ULN. 11. Total bilirubin ≤1.5 mg/dL unless elevated due to known Gilbert's syndrome. 12. Creatinine ≤1.5 ULN. 13. Serum potassium and magnesium at least at the lowest limit of normal (LLN), before every IMP administration. If it is below the LLN, supplementation is permissible. 14. Female study participants of child-bearing potential and their partners, and male study participants who intend to be sexually active with a woman of child-bearing potential, must be willing to use at least two (2) highly effective forms of contraception. This should start from the time of study enrollment and continue throughout IMP administration. For female study participants of child-bearing potential this must continue using contraception for at least six (6) months after the last administration of the IMP. Female study participants should be willing to have a pregnancy test performed at screening, ≤ 1 day prior to day 1 of each IMP administration and at study treatment discontinuation. Male study participants who are sexually active with a woman of child-bearing potential should also use a condom during treatment and for at least ninety (90) days after the last administration of IMP. Vasectomized males are considered fertile; therefore, vasectomized partners and patients must be willing to use a secondary method of effective birth control. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Exclusion Criteria Phase 1 and Phase 2 portions of Study: To be eligible to participate in the trial, a patient cannot meet any of the following exclusion criteria: 1. Patients with primary central nervous system (CNS) cancer. 2. Patients with QTc interval (Fridericia's formula) \>450 msec. 3. Patients who are on treatment with drugs known to prolong the QT/QTc interval. 4. Patients who are being treated with Valproic Acid for any of its indication (epilepsy, mood disorder). 5. Any serious medical condition that interferes with adherence to trial procedures. 6. Prior history of solid tumor malignancy diagnosed within the last three (3) years of study enrollment excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment) 7. Pregnant or breast feeding females. 8. New York Heart Association (NYHA) stage III/IV congestive heart failure, arrhythmias not adequately controlled, or other significant co-morbidities \[e.g. active infection requiring systemic therapy, history of human immunodeficiency virus (HIV) infection, or active Hepatitis B or Hepatitis C\]. 9. Use of other investigational agents within 28 days prior to the first dose of study drug, provided the patient has recovered from any related toxicities ≥Grade 1. 10. Steroid treatment within seven (7) days prior to trial treatment. Patients that require intermittent use of bronchodilators, topical steroids or local steroid injections will not be excluded from the study. Patients who have been stabilized to 10 mg Prednisolone orally (PO) once daily (QD) (or equivalent), daily (or less) at least seven (7) days prior to IMP administration are allowed. Phase 2: Patients must meet the cohort-specific inclusion/exclusion criteria in addition to the general inclusion/exclusion criteria for Phase 1 and Phase 2 study listed above. Cohort 1: Relapsed/Refractory small cell lung cancer (SCLC) 1. Histologically or cytologically confirmed limited or extensive disease stage of SCLC. 2. Must have received at least 1 line of prior combination chemotherapy or biological therapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient. 3. At least 28 days should have elapsed since prior treatment as long as the patient has recovered from any related toxicities to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies). 4. Prior radiotherapy is acceptable provided the patient has recovered from any radiotherapy related acute toxicities. 5. The disease should be progressing during or relapsing after the previous treatment. 6. Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion. Cohort 2: Relapsed/Refractory Soft Tissue Sarcoma (STS) 1. Histologically confirmed diagnosis of advanced, unresectable, or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy excluding: neuroblastoma, GIST, embryonal rhabdomyosarcoma, Kaposi sarcoma, chondrosarcoma, osteosarcoma or Ewing's sarcoma. 2. Must have received at least one prior line prior line chemotherapy or biological therapy regimen and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient. At least twenty-eight (28) days should have elapsed since prior chemotherapy, as long as the patient recovered from any related toxicities to ≤ Grade 1 (or ≤Grade 2 for any symptomatic neuropathy or endocrinopathies). 3. The disease should be progressing during or relapsing after the previous treatment. 4. Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion. Cohort 3: Relapsed/Refractory Triple Negative Breast Cancer (TNBC) 1. Histologically or cytologically confirmed locally advanced or metastatic Triple Negative Breast Cancer. Proven human epidermal growth factor receptor 2 (HER2) negative by immunohistochemistry (INH) or in situ hybridization (ISH) per per American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines. 2. Must have received at least one (1) line of chemotherapy or biological therapy and no other standard therapy with proven clinical benefit was available or recommended based on the Investigator's individual risk-benefit assessment for the subject. 3. At least three (3) weeks should have elapsed since prior chemotherapy as long as the subject recovered from acute toxicity of previous therapies to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies). 4. Prior radiotherapy was acceptable provided it was administered at least four (4) weeks (two (2) weeks for palliative, limited field radiation therapy) prior to starting treatment on this study and the subject recovered from any radiotherapy related acute toxicities. 5. The disease had to be progressing during or relapsing after the previous treatment. 6. Presence of measurable disease as defined by RECIST version 1.1. Tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, were usually not considered measurable unless there had been demonstrated progression in the lesion. Cohort 4: Patient Population: Relapsed/Refractory Ovarian Cancer (OC) 1. Histologically or cytologically confirmed advanced ovarian cancer: epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube cancer (excluding borderline ovarian cancer, MMMT) of high grade serous histology, or high grade endometrioid cancer, that is resistant or refractory to platinum therapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient. Clear cell carcinomas are excluded. Patients with primary platinum refractory disease (failure to respond to initial platinum treatment or relapse within four (4) weeks) and patients with primary platinum resistant disease (progression within six (6) months of completing first line platinum-based therapy) are excluded from the study. 2. At least twenty eight (28) days should have elapsed since prior chemotherapy as long as the patient recovered from acute toxicity of previous therapies to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies). 3. The disease should be progressing during or relapsing after the previous treatment. 4. Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion. Cohort 5: Relapsed/Refractory Endometrial Cancer (EC) 1. Histologically or cytologically confirmed locally advanced or metastatic endometrial cancer (excluding leiomyosarcoma and carcinosarcoma) 2. Must have received at least one (1) line of chemotherapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient. At least three (3) weeks should have elapsed since prior chemotherapy or 5 half-lives, whichever is shorter, as long as the patient recovered from acute toxicity of previous therapies to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies). 3. Prior radiotherapy is acceptable provided it was administered at least four(4) weeks (two (2) weeks for palliative, limited field radiation therapy) prior to starting treatment on this trial and recovered from any radiotherapy related acute toxicities. 4. The disease should be progressing/relapsed during or after the previous treatment. 5. Presence of measurable disease as defined by RECIST version 1.1. Tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, were usually not considered measurable unless there had been demonstrated progression in the lesion.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Drug: Tinostamustine 60mg/m2 over 30min
    label
    Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 min) cohort 1
    type
    EXPERIMENTAL
  2. intervention Names
    1. Drug: Tinostamustine 80mg/m2 over 30min
    label
    Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 min) cohort 2
    type
    EXPERIMENTAL
  3. intervention Names
    1. Drug: Tinostamustine 100mg/m2 over 30min
    label
    Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 min) cohort 3
    type
    EXPERIMENTAL
  4. intervention Names
    1. Drug: Tinostamustine 60mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 min) cohort 4
    type
    EXPERIMENTAL
  5. intervention Names
    1. Drug: Tinostamustine 80mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 min) cohort 5
    type
    EXPERIMENTAL
  6. intervention Names
    1. Drug: Tinostamustine 100mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 min) cohort 6
    type
    EXPERIMENTAL
  7. intervention Names
    1. Drug: Tinostamustine 80mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Small Cell Lung Cancer (SCLC) cohort
    type
    EXPERIMENTAL
  8. intervention Names
    1. Drug: Tinostamustine 80mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Soft Tissue Sarcoma (STS) cohort
    type
    EXPERIMENTAL
  9. intervention Names
    1. Drug: Tinostamustine 80mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Triple Negative breast Cancer (TNBC) cohort
    type
    EXPERIMENTAL
  10. intervention Names
    1. Drug: Tinostamustine 80mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Ovarian Cancer (OC) cohort
    type
    EXPERIMENTAL
  11. intervention Names
    1. Drug: Tinostamustine 80mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Endometrial Cancer (EC) cohort
    type
    EXPERIMENTAL
  12. intervention Names
    1. Drug: Tinostamustine 60mg/m2 over 60min
    label
    Tinostamustine (EDO-S101) - Sub study 1 (SS1)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 min) cohort 1
    description
    Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
    name
    Tinostamustine 60mg/m2 over 30min
    other Names
    1. EDO-S101
    type
    DRUG
  2. arm Group Labels
    1. Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 min) cohort 2
    description
    Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
    name
    Tinostamustine 80mg/m2 over 30min
    other Names
    1. EDO-S101
    type
    DRUG
  3. arm Group Labels
    1. Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 min) cohort 3
    description
    Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
    name
    Tinostamustine 100mg/m2 over 30min
    other Names
    1. EDO-S101
    type
    DRUG
  4. arm Group Labels
    1. Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 min) cohort 4
    2. Tinostamustine (EDO-S101) - Sub study 1 (SS1)
    description
    Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
    name
    Tinostamustine 60mg/m2 over 60min
    other Names
    1. EDO-S101
    type
    DRUG
  5. arm Group Labels
    1. Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 min) cohort 5
    2. Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Endometrial Cancer (EC) cohort
    3. Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Ovarian Cancer (OC) cohort
    4. Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Small Cell Lung Cancer (SCLC) cohort
    5. Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Soft Tissue Sarcoma (STS) cohort
    6. Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Triple Negative breast Cancer (TNBC) cohort
    description
    Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
    name
    Tinostamustine 80mg/m2 over 60min
    other Names
    1. EDO-S101.
    type
    DRUG
  6. arm Group Labels
    1. Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 min) cohort 6
    description
    Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
    name
    Tinostamustine 100mg/m2 over 60min
    other Names
    1. EDO-S101
    type
    DRUG
  7. arm Group Labels
    1. Tinostamustine (EDO-S101) - Sub study 2 (SS2)
    description
    Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 80 minutes on Days (D) 1 and 15 of each 28-day cycle.
    name
    Tinostamustine 80mg/m2 over 80min
    other Names
    1. EDO-S101
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SEQUENTIAL
intervention Model Description
In phase 1 (dose escalation phase) of the study, subjects were allocated sequentially. In phase 2, subjects were allocated in parallel to the various arms (cohorts) based on their cancer specifics. In the substudies 1 and 2, subjects were allocated into a single group in each substudy. Overall, the study model is described as Sequential as the study proceeded in phases.
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
71
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    All TEAEs was reported from the first dose of study drug through the time of study drug discontinuation (at any time or Day 28 of the last treatment Cycle). All treatment-related TEAEs was followed until resolution or stabilization. For the purpose of regulatory reporting requirements, causal relationships of definite, probable, and possible was considered treatment-related. Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03. (June 2010).
    measure
    Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1
    time Frame
    From each patient's time of first dose administration to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 6 months.
  2. description
    The Clinical Benefit Response Rate is calculated as the number of patients with Clinical Benefit Response divided by number of patients in the FAS (in the respective cohort). Clinical Benefit Response is defined as patients achieving stable disease with a duration of at least 12 weeks (84 days). Summary subjects analysed were 36.
    measure
    Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2
    time Frame
    From start treatment and assessed after every 2 cycles until determination of stable disease and follow up for up to 84 days.
  3. description
    QTcF: corrected QT interval \[QTc\] using Fridericia's formula) and other electrocardiogram (ECG) parameters in subjects with solid tumours who have progressed after at least 1 line of therapy and for whom no other standard therapy with proven clinical benefit is available. Within each cycle a Change from baseline (CfB) is calculated for QTcF relative to the baseline value of day 1 of the cycle. QTcF CfB= QTcF Post-dose value - QTcF pre-dose value of D1 ECG Parameters: 4-hours ECG holter monitoring in C1 and ECGs during EDO-S101 administration. Continuous variables the mean and standard deviation are presented together with the total number of observations and the number of missing and non-missing values.
    measure
    Highest Change From Baseline in QTcF in Sub-studies
    time Frame
    From cycle 1 and at every cycle on treatment days D1 and D15, assessed pre-dose and post-start of infusion at 30 and 80mins (Substudy 2 - up to 6 months) and 30, 60, 90, 120 and 180mins (substudy 1 - up to 6 months).
secondary Outcomes
  1. description
    Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03, June 2010, with the exception that assessment of QTc prolongations constituting adverse events (AEs) of special interest were based on NCI CTCAE version 5.0, November 2017. All subjects who received at least 1 dose of study treatment were included in the Safety Population. Safety analyses were performed on data from all subjects in the Safety Population. Adverse events are reported on a patient basis. The percentages are calculated using the number of patients in the Safety Analysis Set as the denominator.
    measure
    Treatment-related Adverse Events on Phase 2 and Sub Studies
    time Frame
    From each patient's time of informed consent to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 8 months
  2. description
    PFS was defined as the number of days between the date of the first dose of treatment of a patient and the first date of disease progression, start of a subsequent anti-cancer therapy, or death of the patient.
    measure
    Progression Free Survival (PFS) Time for Phase 2 and Sub Studies
    time Frame
    From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 26 months.
  3. description
    Overall survival is defined as the number days between the date of the first dose of treatment and the date of death. If no date of death is recorded the Overall Survival time is censored at the Last available visit date. Phase 2: To determine the overall survival (OS) time for subjects with solid tumours. SS1:To determine the overall survival (OS) time for subjects who received 60 mg/m2 of EDO-S101 during a 60-minute Infusion. SS2: To determine the overall survival (OS) time for subjects who received 80 mg/m2 of EDO-S101 during a 80-minute Infusion.
    measure
    Overall Survival (OS) Time for Phase 2 and Sub Studies
    time Frame
    From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 42 months.
  4. description
    The duration of objective response is measured from the date of the first tumor response assessment with an Investigator's Overall Response of CR or PR (whichever status is recorded first) until the date of progression or death. DoR is presented by subject.
    measure
    Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies
    time Frame
    From patient's first overall response of CR or PR, until disease progression/subsequent anti-cancer therapy/death from any cause, up to 24 months.
  5. description
    To determine the objective response rate (ORR) and the clinical benefit rate (CBR \[Complete Response (CR), Partial Response (PR) plus durable Stable Disease (SD)\]) in Sub Studies. SD was regarded as durable if, after observing SD, the first observation of PD was at least 84 days after the start of study treatment.
    measure
    Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies
    time Frame
    From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months)
  6. description
    Duration of SD, was defined as the number of days between the date of the first dose of treatment and the first date of disease progression or death. SD was regarded as durable if, after observing SD, the first observation of progression disease was at least 84 days after the start of study treatment.
    measure
    Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies.
    time Frame
    From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months).
  7. measure
    Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies
    time Frame
    Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
  8. measure
    Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies.
    time Frame
    Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
  9. measure
    Summary of Tmax in in Phase 2 and Sub Studies.
    time Frame
    Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
  10. measure
    Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies
    time Frame
    Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
  11. measure
    Summary of Half-life of Tinostamustine in Phase 2 and Substudies.
    time Frame
    Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Full study description
brief Summary
Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor designed to improve drug access to deoxyribonucleic acid (DNA) strands, induce DNA damage and counteract its repair in cancer cells. The main purpose of this study is to assess the safety, tolerability and efficacy of Tinostamustine in subjects with advanced solid tumours. Subjects will be given Tinostamustine via intravenous infusion on Days 1 and 15 of a 4-week cycle, the dose and infusion time will vary depending on the phase of the study.
detailed Description
The study consists of 2 phases and 2 sub-studies: This study is a multi-centre, open-label phase 1/2 study of single agent EDO-S101 in subjects with advanced solid tumours. Phase 1 part of the study is designed to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and the Pharmacokinetic (PK) of EDO-S101 as a single agent in patients with solid tumours who have progressed after at least one (1) line of therapy and for whom no other standard therapy with proven clinical benefit is available. Phase 2 part of the study is designed to evaluate the overall response rate (ORR) of the RP2D, plus the rate of patients with stable disease (SD) at 4 or 6 months, depending on the type of solid tumour. The RP2D was determined after phase 1 to be 80 mg/m2 of EDO-S101 administered over 1 hour on Day 1 and Day 15 of each 4-week treatment cycle. In addition, two sub-studies are designed to better characterize the effect of EDO-S101: one at a dose of 60 mg/m2 administered over 60 minutes and the second at a dose of 80 mg/m2 administered over 80 minutes on cardiac repolarization (QTc) and other ECG parameters in the subjects with solid tumours. Subjects were eligible for these studies if they had a histologically confirmed solid tumour, signed informed consent and met the inclusion/exclusion criteria. After providing informed consent, subjects were screened, and all procedures were performed as per protocol.
Source references
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-1336d216cbd1bbff780dac70
      edge id
      nct-edge-63bc049447049a7eba9a
      requested nct id
      NCT03345485
      primary nct id
      NCT03345485
      source kind
      ctgov_condition_query
      source record id
      Source null
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      21b84c01b125d04528c86b8a2e80343ce07b200dcda51c3b1328a536daf43d89
      payload sha256
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      payload
      clinical indication matching status
      condition_index_match_asserted_by_registry_not_reviewed
      end exclusive
      true
      id
      nct-edge-63bc049447049a7eba9a
      link basis
      returned_by_explicit_condition_and_posted_results_filter_query
      nct id
      NCT03345485
      occurrences
      1. context exact
        NCT03345485
        end
        11
        exact text
        NCT03345485
        start
        0
      offset unit
      unicode_code_points
      query cond
      Uterine Sarcoma
      query disease state id
      ds-uterine-sarcoma
      source file
      /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-uterine-sarcoma-000.json
      source file sha256
      21b84c01b125d04528c86b8a2e80343ce07b200dcda51c3b1328a536daf43d89
      source json pointer
      /studies/57/protocolSection/identificationModule/nctId
      source kind
      ctgov_condition_query
      source record id
      Source null
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      5ed292d3e25b9800b74575f613c9c630df74f21e897b509ea3ecc582bf3aa25e

    Preserved source evidence · Not medical advice