Patient case: 54-year-old female with Breast cancer. Genetic variant: PTEN Loss. Other conditions: Congestive Heart Failure.

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

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: 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

Relevance to patient case: not relevant