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NCT02489903 · REGISTRY CONDITION SEARCH

RRx-001 in Lung Cancer, Ovarian Cancer and Neuroendocrine Tumors Prior to Re-administration of Platinum Based Doublet Regimens (QUADRUPLE THREAT)

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

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2025-03-17

This study is designed to explore the potential of the epigenetic agent RRx-001 to sensitize patients who previously received and now have failed a platinum based doublet regimen. RRx-001 is administered with autologous blood once weekly followed by or in combination with reintroduction of platinum-based doublet therapy.

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

Overall Survival

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Disease Control Rate (DCR)

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outcome · POSTED

Progression Free Survival (PFS)

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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 Criteria * Patients must have histologically or cytologically confirmed advanced or metastatic: * Resistant/Refractory Small Cell Carcinoma (SCC) patients in 3rd line or beyond that have previously received platinum or patients in 2nd line with platinum-refractory or platinum-resistant disease * EGFR mutated non-small cell lung cancer (NSCLC) that has previously received a first line platinum doublet and all applicable EGFR TKIs * Epithelial Ovarian Cancer (EOC), fallopian tube or primary peritoneal cancer and Malignant Mixed Mullerian Tumor (MMMT) of the ovary or uterus. Excludes other non-epithelial ovarian tumors and ovarian tumors with low malignant potential. Patients must have previously received a platinum based regimen for advanced/metastatic disease or have platinum resistant or refractory disease defined as relapse within 6 months. EOC - specific criteria: Patients who progress or have stable disease during first-line treatment or who relapse within 1 month are considered to be 'platinum-refractory'. Patients who respond to primary treatment and relapse within 6 months are considered 'platinum-resistant', and patients who relapse more than 6 months after completion of initial therapy are characterized as 'platinum-sensitive'. Patients who relapse 6-12 months following the end of their initial regimen are classified as 'partially sensitive'. Platinum sensitive patients may be enrolled but must have failed or declined all other lines of FDA approved therapy * High-Grade Neuroendocrine Carcinoma (HGNEC), any organ of origin, including a pathology of neuroendocrine features, in patients previously been treated with chemotherapy Although neuroendocrine tumors may be classified differently based on organ of origin, in the context of this protocol they are defined as high grade on the basis of either 1. Aggressive clinical behavior requiring previous treatment with chemotherapy even if histologic features such as the Ki67 index or mitotic rate corresponds with low or intermediate grade. 2. Histologic features: (a) Neuroendocrine tumors of lung origin are considered high grade if in any part of the tumors, there are \>10 mitoses/2mm2 or 10 high power field (HPF). Large zones of necrosis are usually present. This includes small cell lung carcinoma and large cell neuroendocrine lung carcinoma. \[SCLC will not enroll in the HGNEC cohort.\] (b)Neuroendocrine tumors of gastroenteropancreatic origin are considered high grade if in any part of the tumors there are either \>20 mitoses/2mm2 or 10 high power field (HPF) OR Ki67. * Radiographically measurable disease by RECIST v1.1 * A washout period of 3-weeks from last treatment. * Patients must have previously received a platinum based regimen for advanced/metastatic disease and progressed or have platinum resistant or refractory disease defined as relapse within 6 months. * Age ≥18 years. * Life expectancy of ≥12 weeks. * ECOG performance status 0-2. * Participants must have adequate organ and marrow function as defined below both prior to administration of RRx-001 and prior to administration of platinum doublet based regimen: * Absolute neutrophil count ≥1,500/mcL * Platelets ≥100,000/mcL (non-transfused platelet count) * Hemoglobin ≥9 g/dL (transfused Hgb allowed) * Creatinine ≤1.5 x the upper limit of normal * Total bilirubin ≤2.0 x the upper limit of normal or \<3.0 xULN if patient has a history of Gilbert's syndrome * AST (SGOT)/ALT (SGPT) ≤5 X institutional upper limit of normal if with liver metastases; ≤2.5 X ULN if no liver metastases * Patient must consent to the access, review and analysis of previous medical and cancer history, including tumor archival tissue (if available) and imaging data by the sponsor or a third party nominated by the sponsor. * Ability to understand and sign a written informed consent document. * Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. * Note: A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been postmenopausal for at least 12 consecutive months Exclusion Criteria * Receiving concurrent investigational therapy * Symptomatic central nervous system metastasis (e.g., patients requiring increasing doses of steroids) * History of needing to permanently discontinue prior platinum doublet-based regimen for toxicity (e.g., cisplatin causing renal impairment, ototoxicity, or severe neuropathy). * Known severe hypersensitivity to the platinum agent (i.e., carboplatin or cisplatin) or prior partner of platinum agent (i.e., etoposide for SCC and HGNEC; nab-paclitaxel, paclitaxel, or pemetrexed for NSCLC; paclitaxel, pegylated liposomal doxorubicin, docetaxel or gemcitabine for ovarian) planned for the platinum therapy period. If the patient has had prior hypersensitivity reaction to the drug partner of platinum, a patient may enroll as long as it is acceptable to treat with platinum and one of the alternative chemotherapy partner agents. * Any significant medical diseases or conditions, as assessed by the investigators and sponsor that would substantially increase the medical risks of participating in this study (i.e., uncontrolled diabetes, NYHA II-IV congestive heart failure, myocardial infarction within 6 months of study, severe chronic pulmonary disease or active uncontrolled infection, uncontrolled or clinically relevant pulmonary edema). * Pregnant or nursing
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    RRx-001 weekly for 3 weeks followed by up to 4 cycles of carboplatin or cisplatin plus etoposide and then RRx-001 and carboplatin or cisplatin (for patients with stable disease (SD) or better at discontinuation of platinum).
    intervention Names
    1. Drug: RRx-001
    2. Drug: Cisplatin
    3. Drug: Etoposide
    4. Drug: Carboplatin
    label
    Small Cell Lung Cancer (Arm 1)
    type
    EXPERIMENTAL
  2. description
    Carboplatin or cisplatin plus etoposide or irinotecan or vinorelbine until progression or intolerable toxicity
    intervention Names
    1. Drug: Cisplatin
    2. Drug: Etoposide
    3. Drug: Carboplatin
    4. Drug: Irinotecan
    5. Drug: Vinorelbine
    label
    Small Cell Lung Cancer (Arm 2)
    type
    ACTIVE_COMPARATOR
  3. description
    RRx-001 weekly for 3 weeks followed by up to 6 cycles of cisplatin or carboplatin plus paclitaxel or nab-paclitaxel or pemetrexed and then RRx-001 maintenance (for patients with stable disease or better at discontinuation of platinum).
    intervention Names
    1. Drug: RRx-001
    2. Drug: Cisplatin
    3. Drug: Carboplatin
    4. Drug: Paclitaxel
    5. Drug: Nab-Paclitaxel
    6. Drug: Pemetrexed
    label
    Non Small Cell Lung Cancer
    type
    EXPERIMENTAL
  4. description
    RRx-001 weekly until progression followed by up to 6 cycles of carboplatin or cisplatin plus etoposide and then RRx-001 maintenance (for patients with stable disease or better at discontinuation of platinum).
    intervention Names
    1. Drug: RRx-001
    2. Drug: Cisplatin
    3. Drug: Etoposide
    4. Drug: Carboplatin
    label
    Neuroendocrine tumors
    type
    EXPERIMENTAL
  5. description
    RRx-001 weekly for 2 weeks followed by 2 cycles of Carboplatin chemotherapy and then RRx-001/Carboplatin maintenance (for patients with stable disease or better at discontinuation of platinum).
    intervention Names
    1. Drug: RRx-001
    2. Drug: Carboplatin
    label
    Ovarian epithelial cancer (Arm 1)
    type
    EXPERIMENTAL
  6. description
    Carboplatin, Etoposide, Doxil, Gemcitabine or Vinorelbine or Taxane until progression or intolerable toxicity
    intervention Names
    1. Drug: Etoposide
    2. Drug: Carboplatin
    3. Drug: Vinorelbine
    4. Drug: Doxil
    5. Drug: Gemcitabine
    6. Drug: Taxane
    label
    Ovarian epithelial cancer (Arm 2)
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Neuroendocrine tumors
    2. Non Small Cell Lung Cancer
    3. Ovarian epithelial cancer (Arm 1)
    4. Small Cell Lung Cancer (Arm 1)
    name
    RRx-001
    type
    DRUG
  2. arm Group Labels
    1. Neuroendocrine tumors
    2. Non Small Cell Lung Cancer
    3. Small Cell Lung Cancer (Arm 1)
    4. Small Cell Lung Cancer (Arm 2)
    name
    Cisplatin
    type
    DRUG
  3. arm Group Labels
    1. Neuroendocrine tumors
    2. Ovarian epithelial cancer (Arm 2)
    3. Small Cell Lung Cancer (Arm 1)
    4. Small Cell Lung Cancer (Arm 2)
    name
    Etoposide
    type
    DRUG
  4. arm Group Labels
    1. Neuroendocrine tumors
    2. Non Small Cell Lung Cancer
    3. Ovarian epithelial cancer (Arm 1)
    4. Ovarian epithelial cancer (Arm 2)
    5. Small Cell Lung Cancer (Arm 1)
    6. Small Cell Lung Cancer (Arm 2)
    name
    Carboplatin
    type
    DRUG
  5. arm Group Labels
    1. Small Cell Lung Cancer (Arm 2)
    name
    Irinotecan
    type
    DRUG
  6. arm Group Labels
    1. Ovarian epithelial cancer (Arm 2)
    2. Small Cell Lung Cancer (Arm 2)
    name
    Vinorelbine
    type
    DRUG
  7. arm Group Labels
    1. Ovarian epithelial cancer (Arm 2)
    name
    Doxil
    type
    DRUG
  8. arm Group Labels
    1. Ovarian epithelial cancer (Arm 2)
    name
    Gemcitabine
    type
    DRUG
  9. arm Group Labels
    1. Ovarian epithelial cancer (Arm 2)
    name
    Taxane
    type
    DRUG
  10. arm Group Labels
    1. Non Small Cell Lung Cancer
    name
    Paclitaxel
    type
    DRUG
  11. arm Group Labels
    1. Non Small Cell Lung Cancer
    name
    Nab-Paclitaxel
    type
    DRUG
  12. arm Group Labels
    1. Non Small Cell Lung Cancer
    name
    Pemetrexed
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
139
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    From the time from enrollment until the time of death from any cause or last follow-up. Patients will be followed clinically as outlined in the treatment schedule and will be followed off study for death.
    measure
    Overall Survival
    time Frame
    From start of treatment through death for up to 64 months from Start of Treatment.
secondary Outcomes
  1. description
    Overall Response Rate (ORR) will be defined as the proportion of patients with a CR or a PR per RECIST v1.1 based upon the best response as assessed; confirmation of response was not required, assessed up to 49 months.
    measure
    Overall Response Rate (ORR)
    time Frame
    Assessed up to 49 months
  2. description
    The percentage of patients who have achieved complete response, partial response and stable disease (as per RECIST v1.1), assessed up to 49 months.
    measure
    Disease Control Rate (DCR)
    time Frame
    Assessed up to 49 months
  3. description
    Progression-free survival (PFS) will be defined as the elapsed time from the from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 49 months.
    measure
    Progression Free Survival (PFS)
    time Frame
    Assessed up to 49 months
Full study description
brief Summary
This study is designed to explore the potential of the epigenetic agent RRx-001 to sensitize patients who previously received and now have failed a platinum based doublet regimen. RRx-001 is administered with autologous blood once weekly followed by or in combination with reintroduction of platinum-based doublet therapy.
detailed Description
This is an open label, four 'cohort' study for administration of RRx-001 with autologous blood once weekly followed by or in combination with reintroduction of platinum-based doublet therapy according to the treatment schedule listed below. Small cell carcinoma and ovarian cohort participants will be randomized to 1 of 2 treatment arms, respectively. Neuroendocrine and NSCLC patients will be enrolled to single arms. Participants with SCC will receive one of the following; RRx-001 followed by platinum doublet chemotherapy or platinum based chemotherapy alone. HGNEC, RRx-001 followed by platinum doublet chemotherapy. NSCLC, RRx-001 followed by platinum doublet chemotherapy. Participants with Platinum Refractory/Resistant Ovarian and MMMT will receive one of the following, RRx-001 followed by platinum doublet chemotherapy or chemotherapy alone. Approximately 213 participants will be enrolled.
Source references
references
  1. citation
    Tomita Y, Oronsky B, Abrouk N, Cabrales P, Reid TR, Lee MJ, Yuno A, Baker J, Lee S, Trepel JB. In small cell lung cancer patients treated with RRx-001, a downregulator of CD47, decreased expression of PD-L1 on circulating tumor cells significantly correlates with clinical benefit. Transl Lung Cancer Res. 2021 Jan;10(1):274-278. doi: 10.21037/tlcr-20-359.
    pmid
    33569311
    type
    DERIVED
  2. citation
    Morgensztern D, Rose M, Waqar SN, Morris J, Ma PC, Reid T, Brzezniak CE, Zeman KG, Padmanabhan A, Hirth J, I Spira A, Trepel JB, Padda SK. RRx-001 followed by platinum plus etoposide in patients with previously treated small-cell lung cancer. Br J Cancer. 2019 Jul;121(3):211-217. doi: 10.1038/s41416-019-0504-8. Epub 2019 Jun 24.
    pmid
    31231122
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice