Birinapant and Carboplatin in Treating Patients and Targeting Recurrent High Grade Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (HGSOC)

NCT02756130 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: 16-000746NCI-2016-00596GODL001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies how well birinapant and carboplatin work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back. Drugs used in chemotherapy, such as birinapant and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Change in percentage of cancer initiating cells

  Will be measured using a 3-dimensional organoid assay; population analysis using flow cytometry to measure the overall percentage of platinum resistant tumor initiating cells and by immunohistochemistry. Percent cellular inhibitor of apoptosis (cIAP) positive and amount of cIAP protein will be computed using either the non parametric Wilcoxon signed rank test or the paired t test if the data follow a normal distribution. Full summary statistics including the mean and median difference and the corresponding 95% confidence bounds will be reported. We will report scatter plots and the non parametric Spearman correlation coefficients among these four measures of platinum resistant tumor initiating cells pre-therapy as well as the post- minus pre-treatment difference.

  Baseline up to 2 years

• Pharmacodynamic analysis of cellular inhibitor of apoptosis (cIAP) protein

  Will measure the level of cIAP protein in pre- versus (vs). post-therapy tumors, measured by quantitative western blot, compared to a purified cIAP standard of known amount loaded on the same gel. Percent cIAP positive and amount of cIAP protein will be computed using either the non parametric Wilcoxon signed rank test or the paired t test if the data follow a normal distribution. Full summary statistics including the mean and median difference and the corresponding 95% confidence bounds will be reported. We will report scatter plots and the non parametric Spearman correlation coefficients among these four measures of platinum resistant tumor initiating cells pre-therapy as well as the post- minus pre-treatment difference.

  Baseline up to 2 years

Secondary Outcomes (1)

• Progression free survival (PFS) assessed using imaging (multiparametric magnetic resonance imaging [MRI] (primary modality of imaging) of computed tomography (CT) and the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

  Start of therapy and progression of disease or death whichever comes first, assessed up to 2 years

Other Outcomes (2)

• Cellular inhibitor of apoptosis (cIAP) expression by immunohistochemistry with patient response to co-therapy

  Up to 2 years

• Cellular inhibitor of apoptosis (cIAP) expression by western blot with patient response to co-therapy

  Up to 2 years

Study Arms (1)

Treatment (birinapant, carboplatin)

EXPERIMENTAL

Patients receive birinapant IV over 30 minutes on days 1 and 8, and carboplatin IV over 30 minutes to 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Birinapant; Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Birinapant DRUG

Given IV

Also known as: TL32711

Treatment (birinapant, carboplatin)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (birinapant, carboplatin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (birinapant, carboplatin)

Pharmacological Study OTHER

Correlative studies

Treatment (birinapant, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have measurable disease by imaging defined as tumor that can be measured \>= 10 mm with multiparametric magnetic resonance imaging (MRI) (primary modality of imaging) or computed tomography (CT) (as an alternative) or \>= 10 mm by caliper on physical examination
• Participant is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to initiation of any screening or study-specific procedures
• The participant must have a histologic diagnosis of recurrent high grade serous ovarian cancer (ovarian, tubal, peritoneal), to be treated with chemotherapy
• Participants must have an image guided biopsy performed to yield fresh tissue for the in vitro organoid bio-assay and two biomarker testing (western blot and immunohistochemistry)
• Only patients with tumors that score positive in the in vitro organoid bio-assay will be enrolled in the clinical trial; patients with tumors that score negative in this bio-assay will be considered screening failures and will not be enrolled in the clinical trial
• Participant must have either no neuropathy (sensory and motor) or neuropathy less than or equal to grade 1
• The participant must have an Eastern Cooperative Oncology Group (ECOG) score between 0 - 2 at screening
• The participant must have a life expectancy of greater than 12 weeks
• Absolute neutrophil count \>= 1,500/mm\^3
• Platelets \>= 100,000/ mm\^3
• Hemoglobin \>= 9 g/dL or equivalent
• Total bilirubin =\< 1.5 ? institutional upper limit of normal (ULN), unless known Gilbert?s syndrome has been diagnosed
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 ? institutional ULN (=\< 5 ? ULN if liver metastasis)
• Serum creatinine =\< 1.5 ? ULN or creatinine clearance \>= 50 mL/min/1.73 m\^2
• Amylase \< ULN

You may not qualify if:

• Patients with tumors that score negative in the in vitro organoid bio-assay will be excluded
• Patients with non-measurable disease \< 10 mm on multiparametric MRI or CT scan will be excluded
• Participants with a secondary malignancy that is progressing or requires active treatment; participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative treatment are not excluded
• Participants who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to birinapant or its constituents
• Participants requiring the use of anti-tumor necrosis factor (anti-TNF) therapies, such as infliximab, or has received treatment with anti-TNF therapies within 5 half-lives of the drug
• Participants with an uncontrolled inter-current illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune disease or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women or women who expect to conceive a child are excluded from the study; breastfeeding should be discontinued if the mother is treated on this study
• Participants who have a known active infection requiring systemic therapy, including human immunodeficiency virus (HIV), hepatitis B, and hepatitis C
• Participants with a history of cranial nerve palsy
• Participant is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is an investigational site or sponsor-investigator staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is granted allowing exception to this criterion for a specific subject
• In the opinion of the investigator, the participant is an unsuitable candidate for this study
• Patients who are taking or anticipate taking any maintenance therapy while actively being treated on protocol or while being followed on protocol will be excluded; an example of this would be maintenance therapy with a Poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitor such as olaparib

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• California Institute for Regenerative Medicine (CIRM): collaborator
• TetraLogic Pharmaceuticals: collaborator
• Alpha Stem Cell Clinic (ASCC): collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

birinapant; 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; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Sanaz Memarzadeh

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2016
• First Posted: April 29, 2016
• Study Start: August 1, 2018
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2021
• Last Updated: May 13, 2025

Record last verified: 2018-08

Locations

US (1)