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

Phase 2

Withdrawn

• Conditions: BRCA1 Mutation; Breast Cancer Stage IV; Ovarian Cancer; BRCA2 Mutation
• Interventions: Drug: Carboplatin; Drug: Eribulin; Drug: Veliparib

• Registration Number: NCT03032614
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

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.

Study Timeline

• Study First Submitted: 2017-01-23
• Study First Submitted QC: 2017-01-23
• Study First Posted: 2017-01-26
• Status Verified: 2017-08
• Study Start: 2017-09-30
• Last Update Submitted: 2017-10-06
• Last Update Posted: 2017-10-10
• Primary Completion: 2019-03-31
• Study Completion: 2020-04-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination of Carboplatin, Eribulin, and Veliparib	Carboplatin	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.
Combination of Carboplatin, Eribulin, and Veliparib	Eribulin	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.
Combination of Carboplatin, Eribulin, and Veliparib	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.

Primary Outcome Measures

Name	Time	Method
Incidence, nature and severity of adverse events and serious adverse events, graded according to NCI - Common Toxicity Criteria for Adverse Events version (4.03)	Approximately 1.5 years	Graded according to NCI - Common Toxicity Criteria for Adverse Events version (4.03)
Tumor response assessed using RECIST 1.1 guidelines	Measured every 6 weeks for 21 day cycles for the duration of study treatment, estimated to be less than one year	Response will be assessed in this study via physical exam and imaging.