NCT03480750 · REGISTRY CONDITION SEARCH

Trial of Trientine Plus Pegylated Liposomal Doxorubicin and Carboplatin in Epithelial Ovarian Cancer

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: 2020-11-10

Epithelial ovarian cancer (EOC) is the leading cause of gynecological malignancy-related deaths worldwide and is a substantial health threat to women. Many patients eventually develop chemoresistant relapsed disease and die despite surgery and combination chemotherapy. Progress in improving the survival in EOC has been slow, despite significant advances in treatment over the past 25 years. Tubal cancer and peritoneal cancer are thought to be similar in their origin, characteristics and treatment strategies. Based upon basic and animal studies, it is thought that copper chelators overcome platinum resistance. Thus, Trientine combined with carboplatin has been used to treat human cancers. The adverse effects (AEs) are acceptable in previously heavily-treated recurrent ovarian cancer patients, however, the treatment responses are limited. Therefore, here the investigators conduct a phase I trial of Trientine®, pegylated doxorubicin and carboplatin to find the dose-limited toxicities, and maximal toxicity dosage, and to explore whether the combination is applicable in epithelial ovarian, tubal and peritoneal cancers.

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 Dose-Limiting Toxicity (DLT)

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outcome · POSTED

Maximum Tolerated Dose, MTD

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outcome · POSTED

Maximum Plasma Concentration [Cmax] of Trientine

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outcome · POSTED

Progression-free Survival

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outcome · POSTED

Overall Survival

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outcome · POSTED

Percentage of Participants With Measurable Tumor Treatment Response Assessed by RECIST Criteria 1.1

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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: * Histologically proved epithelial ovarian cancer, tubal cancer, and primary peritoneal cancer after surgical staging or debulking surgery * The first relapse within 1 year after the completion of primary platinum-based chemotherapy (partially platinum-resistant/-sensitive) or disease progression during primary chemotherapy (platinum-refractory). * Eastern Cooperative Oncology Group (ECOG) performance status 2 or less * Adequate bone marrow function (absolute neutrophil count ≥ 1,500/μl, hemoglobin ≥ 9.0 g/dL and platelet count ≥ 100,000/μl) * Serum creatinine ≤ 1.5 mg/dL or a calculated creatinine clearance of at least 50 mL/min, total serum bilirubin ≤ 5.0 mg/dL * Alanine transaminase (ALT) or aspartate aminotransferase (AST) ≤ 5 × upper normal limit * Patients with reproductive potential had to agree to use an effective method of birth control prior to study entry for the duration of the study participation * If there was no available therapy that prolonged survival for at least 3 months Exclusion Criteria: * Patients who have metastasis to the central nervous system * Patients who have other malignancies within 5 years prior to study entry with the exception of carcinoma in situ of the cervix uteri and non-melanoma skin cancers * Patients who are receiving concurrent chemotherapy * Patients who have not recovered from surgery within 4 weeks of the study; * Patients with a clinically significant medical condition that could be aggravated by treatment or that cannot be controlled * Patients with medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk * Patients with known anaphylactic response or severe hypersensitivity to study drugs or their analogs * Pregnant or lactating women * Patients with any evidence of difficulty swallowing, intestinal obstruction or malabsorption disorder interfering with nutrition * Patients who were unwilling or unable to provide informed consent
gender Based: true
gender Description: female gender for gynecologic cancer (epithelial ovarian cancer, tubal cancer, and primary peritoneal cancer)
healthy Volunteers: false
maximum Age: 75 Years
minimum Age: 20 Years
sex: FEMALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
trientine dihydrochloride PO daily (in different dose levels) plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1
intervention Names
Drug: trientine dihydrochloride
Drug: pegylated liposomal doxorubicin
Drug: carboplatin
label
trientine with chemotherapy
type
EXPERIMENTAL

interventions

arm Group Labels
trientine with chemotherapy
description
trientine dihydrochloride 300MG/CAPSUE PO daily (in different dose levels)
name
trientine dihydrochloride
other Names
pegylated liposomal doxorubicin
carboplatin
type
DRUG
arm Group Labels
trientine with chemotherapy
description
pegylated liposomal doxorubicin 40mg/m2 IV D1
name
pegylated liposomal doxorubicin
other Names
trientine dihydrochloride
carboplatin
type
DRUG
arm Group Labels
trientine with chemotherapy
description
carboplatin AUC 4 IV D1
name
carboplatin
other Names
trientine dihydrochloride
pegylated liposomal doxorubicin
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 18
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
(1) Grade 4 neutropenia (ANC \<500/cumm\^3) or thrombocytopenia ≧7 days; (2) Hematologic toxicities ≧ Grade 3, eg. febrile neutropenia \<1,000/cumm\^3, or platelet count \<25,000/cumm\^3 with hemorrhage ≧ 7 days; (3) Non-hematologic toxicities ≧ grade 3, eg. ALT or AST, ≧ 7days; other non-hematologic toxicities ≧ grade 3 (except alopecia, non-chemotherapy related nausea/vomiting); (4) Neurologic toxicities ≧ grade 2, eg. dizziness, or lethargy ≧ 3 days
measure
Number of Participants With Dose-Limiting Toxicity (DLT)
time Frame
36 days

secondary Outcomes

description
'3+3' study design. MTD will be defined at the dose level of trientine prior to the level with DLT events ≧ 2/6 participants.
measure
Maximum Tolerated Dose, MTD
time Frame
within 36 days after the start of Trientine
description
Trientine (TETA) prior to and within 24 hrs and 7 days after trientine
measure
Maximum Plasma Concentration [Cmax] of Trientine
time Frame
0, 10mins, 30mins, 60mins, 90mins, 120mins, 4h, 6h, 24h, 148h, 150h, 153h, 156h post 1st dose of trientine
description
Time is calculated from the diagnosis to the last follow-up date if no disease progression , or the date of disease progression after the last treatment cycle of the study drugs
measure
Progression-free Survival
time Frame
36 months
description
Time is calculated from the diagnosis to the date of the last follow-up date if no death event, or the date of death.
measure
Overall Survival
time Frame
36 months
description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan
measure
Percentage of Participants With Measurable Tumor Treatment Response Assessed by RECIST Criteria 1.1
time Frame
176 days

Full study description

brief Summary: Epithelial ovarian cancer (EOC) is the leading cause of gynecological malignancy-related deaths worldwide and is a substantial health threat to women. Many patients eventually develop chemoresistant relapsed disease and die despite surgery and combination chemotherapy. Progress in improving the survival in EOC has been slow, despite significant advances in treatment over the past 25 years. Tubal cancer and peritoneal cancer are thought to be similar in their origin, characteristics and treatment strategies. Based upon basic and animal studies, it is thought that copper chelators overcome platinum resistance. Thus, Trientine combined with carboplatin has been used to treat human cancers. The adverse effects (AEs) are acceptable in previously heavily-treated recurrent ovarian cancer patients, however, the treatment responses are limited. Therefore, here the investigators conduct a phase I trial of Trientine®, pegylated doxorubicin and carboplatin to find the dose-limited toxicities, and maximal toxicity dosage, and to explore whether the combination is applicable in epithelial ovarian, tubal and peritoneal cancers.
detailed Description: Epithelial ovarian cancer, tubal, primary peritoneal cancers are lethal gynecologic malignances, with a 5-year survival rate below 25% for patients diagnosed with stage III-IV. Most advanced stage patients respond to cytoreductive surgery and platinum-based chemotherapy; however, \>70% of women relapse, and platinum-resistant EOC is uniformly fatal. Physicians often increase the dosage of cytotoxic agents, or use single or combination second-line agents to overcome the drug resistance. Nevertheless, second-line chemotherapy sometimes may not achieve the expected cytotoxic effect and drug resistance may lead to cancer-specific death. Overcoming resistance is an important strategy for improving the therapeutic efficacy in cisplatin-containing cancer chemotherapy. Cu homeostasis in human cells involves the inter-regulatory circuitry composed of Cu, the high-affinity Cu transporter (hCtr1) and transcription factor Sp1. Human copper transporter 1 (htr1) in humans are also involved in the import of antitumor agent cisplatin (Cp). Earlier the investigators also discovered that the magnitude of hCtr1 expression by Cu chelators depends upon the basal levels of hCtr1 expression, and that high levels of hCtr1 expression can be modulated through Cu deprivation in Cp-resistant (CpR) cells, providing a molecular basis for the development of Cu chelators as Cp resistance reversal agents in the clinical settings. D-penicillamine and Cp act synergistically to inhibit tumor growth. The investigators conduct this trial with combination agents, including LipoDox®, carboplatin and Trientine®, to develop the clinical application of copper chelator in conjunction with cytotoxic agents to conquer platinum-resistance. This trial is practical and is of perspective.

Source references

references

citation
Huang YF, Kuo MT, Liu YS, Cheng YM, Wu PY, Chou CY. A Dose Escalation Study of Trientine Plus Carboplatin and Pegylated Liposomal Doxorubicin in Women With a First Relapse of Epithelial Ovarian, Tubal, and Peritoneal Cancer Within 12 Months After Platinum-Based Chemotherapy. Front Oncol. 2019 May 24;9:437. doi: 10.3389/fonc.2019.00437. eCollection 2019.
pmid
31179244
type
DERIVED

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice