Clinical trial NCT03032614: Combination of Carboplatin, Eribulin and Veliparib in Stage IV Cancer Patients
Official title: Phase II Clinical Trial on the Combination of Carboplatin, Eribulin and Veliparib in Stage IV Cancer Patients With Homologous Recombination Deficiency
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Cancer Stage IV
Ovarian Cancer
BRCA1 Mutation
BRCA2 Mutation
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2017-01-26
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence, nature and severity of adverse events and serious adverse events, graded according to NCI - Common Toxicity Criteria for Adverse Events version (4.03)
timeFrame: Approximately 1.5 years
measure: Tumor response assessed using RECIST 1.1 guidelines
timeFrame: Measured every 6 weeks for 21 day cycles for the duration of study treatment, estimated to be less than one year
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: UT Health San Antonio
name: Virginia Kaklamani, MD
role: PRINCIPAL_INVESTIGATOR
References: