Combination of Carboplatin, Eribulin and Veliparib in Stage IV Cancer Patients

NCT ID: NCT03032614

Last Updated: 2017-10-10

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-30
• Study Completion Date: 2020-04-30

Brief Summary

This is a phase II clinical trial of the combination of carboplatin, eribulin, and Veliparib.

Detailed Description

This is a Phase II, non-randomized, open-label, Clinical Trial on the Combination of Carboplatin, Eribulin, and Veliparib in Patients with BRCA-related Cancers.

Conditions

Breast Cancer Stage IV; Ovarian Cancer; BRCA1 Mutation; BRCA2 Mutation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination of Carboplatin, Eribulin, and Veliparib

Eribulin will be administered intravenously (IV) on days 1 and 8 of each cycle at a dose of 1.1 mg/m2 over a 2-5 minute time period; on cycle day 1. Carboplatin will be administered intravenously at a dose of AUC 5 on day 1 of each cycle, over 30 min, immediately following eribulin infusion, per institutional guidelines. Veliparib will be given at 120 mg bid (two times a day), on days 2-12 for the first cycle of the safety run-in period and thereafter at 240 mg bid.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Carboplatin is a second generation tetravalent organic platinum compound. Similar to cisplatin, carboplatin produces predominantly interstrand DNA crosslinks as opposed to DNA-protein crosslinks. Carboplatin is cell-cycle non-specific.

Eribulin

Intervention Type: DRUG

Eribulin Mesylate is a synthetic halichondrin analog.

Veliparib

Intervention Type: DRUG

Veliparib is a potent PARP inhibitor that delays the repair of DNA damage induced by chemotherapeutics.

Interventions

Carboplatin

Carboplatin is a second generation tetravalent organic platinum compound. Similar to cisplatin, carboplatin produces predominantly interstrand DNA crosslinks as opposed to DNA-protein crosslinks. Carboplatin is cell-cycle non-specific.

Intervention Type: DRUG

Eribulin

Eribulin Mesylate is a synthetic halichondrin analog.

Intervention Type: DRUG

Veliparib

Veliparib is a potent PARP inhibitor that delays the repair of DNA damage induced by chemotherapeutics.

Intervention Type: DRUG

Other Intervention Names

Paraplatin; Halaven; E7389; ABT-888

Eligibility Criteria

Inclusion Criteria

• Patients must have archival biopsy specimens (preferably from metastatic disease) available for research tests. If a suitable biopsy specimen is not available, patients will be asked to undergo a research biopsy to procure tissue
• Patients must be >/= 18 years
• Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation
• Patients must have an ECOG performance status 0-1
• Patients may have had a prior diagnosis of cancer if it has been > 5 years since their last treatment for that cancer
• Patients must have normal organ and marrow function as defined below:

• Leukocytes ≥ 3,000/uL
• Absolute neutrophil count ≥ 1,500/uL
• Platelets ≥ 100,000/uL
• Creatinine within normal limits or creatinine clearance ≥30
• Patients must be able to swallow and retain oral medication
• Patients who were receiving prior systemic therapy: Prior treatment related side effects must have resolved to < Grade 2 severity (except alopecia and infertility)
• All patients must have given signed, informed consent prior to registration on study
• Patients must have stage IV breast or stage III and IV ovarian cancer (including platinum sensitive disease)
• Patients must have BRCA1/2 deleterious mutations, PTEN deficiency, or cancer with a high HRD score as assessed by Myriad's assay
• Patients must have measurable disease per RECIST 1.1 criteria (see above for definition)
• Patients may not have received more than 3 chemotherapeutic regimens for metastatic disease
• Patients may not have received treatment with prior carboplatin, eribulin or a PARP inhibitor

Exclusion Criteria

• Women who are pregnant or lactating are not eligible
• Patients who are undergoing concomitant radiotherapy are not eligible
• Patients who are receiving any other investigational agents or concurrent anticancer therapy are not eligible
• Previous systemic treatment is allowed with a 21 day washout period prior to registration
• Patients who are taking any herbal (alternative) medicines are not eligible. Patients must be off any such medications by the time of registration
• Patients with known brain metastases are not eligible for participation unless the following are met:

• Brain metastases are treated (either with surgical excision, stereotactic radiosurgery or radiotherapy and have been stable for at least 4 weeks (MRI documented)
• Patient is asymptomatic and has discontinued corticosteroids if taken for that purpose
• Patients with any of the following conditions or complications are NOT eligible for participation:

• GI tract disease resulting in an inability to take oral medication
• Malabsorption syndrome
• Require IV alimentation
• History of prior surgical procedures affecting absorption
• Uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
• Hypersensitivity of any of the components of Veliparib, carboplatin, eribulin
• History of significant neurological (no neuropathy > Grade 2) or psychiatric disorders.
• Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).
• Significant non-neoplastic renal disease.
• Immunocompromised subjects, including subjects known to be infected with human immunodeficiency virus (HIV).
• Uncontrolled endocrine diseases (e.g., diabetes mellitus, hypothyroidism or hyperthyroidism, adrenal disorder) i.e., requiring relevant changes in medication within the last month or hospital admission within the last three months
• Active infection requiring systemic therapy.
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment.
• Prolongation of QTc interval to > 480 msec when electrolytes balance is normal.
• Major surgery within 4 weeks prior to the first dose of study drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Virginia G. Kaklamani

Clinical Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Virginia Kaklamani, MD

Role: PRINCIPAL_INVESTIGATOR

UT Health San Antonio

Other Identifiers

17-166H

Identifier Type: OTHER

Identifier Source: secondary_id

CTMS#16-0133

Identifier Type: -

Identifier Source: org_study_id