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

NCT03480750 | Completed Phase 1 Results

• 1 other identifier: BR-100-074
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ovarian Neoplasms Malignant (Excl Germ Cell); Peritoneal Carcinoma; Fallopian Tube Cancer

Keywords

Copper chelator; Epithelial ovarian cancer; Tubal cancer; Peritoneal cancer; Trientine; Pegylated liposomal doxorubicin; Carboplatin

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-Limiting Toxicity (DLT)

  (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

  36 days

Secondary Outcomes (5)

• Maximum Tolerated Dose, MTD

  within 36 days after the start of Trientine

• Maximum Plasma Concentration [Cmax] of Trientine

  0, 10mins, 30mins, 60mins, 90mins, 120mins, 4h, 6h, 24h, 148h, 150h, 153h, 156h post 1st dose of trientine

• Progression-free Survival

  36 months

• Overall Survival

  36 months

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

  176 days

Study Arms (1)

trientine with chemotherapy

EXPERIMENTAL

trientine dihydrochloride PO daily (in different dose levels) plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1

Drug: trientine dihydrochloride; Drug: pegylated liposomal doxorubicin; Drug: carboplatin

Interventions

trientine dihydrochloride DRUG

trientine dihydrochloride 300MG/CAPSUE PO daily (in different dose levels)

Also known as: pegylated liposomal doxorubicin, carboplatin

trientine with chemotherapy

pegylated liposomal doxorubicin DRUG

pegylated liposomal doxorubicin 40mg/m2 IV D1

Also known as: trientine dihydrochloride, carboplatin

trientine with chemotherapy

carboplatin DRUG

carboplatin AUC 4 IV D1

Also known as: trientine dihydrochloride, pegylated liposomal doxorubicin

trientine with chemotherapy

Eligibility Criteria

• Age: 20 Years - 75 Years
• Gender Eligibility Details: female gender for gynecologic cancer (epithelial ovarian cancer, tubal cancer, and primary peritoneal cancer)
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Trientine; liposomal doxorubicin; Carboplatin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Coordination Complexes

Results Point of Contact

• Title: Dr. Yu-Fang Huang
• Organization: National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University

yufangh@mail.ncku.edu.tw

886 6 2353535

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: March 29, 2018
• Study Start: September 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: December 1, 2019
• Last Updated: November 10, 2020
• Results First Posted: November 10, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share