Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer

NCT01104259 | Completed Phase 1 DMC

• 3 other identifiers: 7161NCI-2010-00356P30CA015704
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of veliparib when given together with cisplatin and vinorelbine ditartrate in treating patients with breast cancer that has returned or spread to other parts of the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and vinorelbine ditartrate, 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. Giving veliparib together with combination chemotherapy may be a better treatment for breast cancer.

Conditions

Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Hereditary Breast/Ovarian Cancer - BRCA1; Hereditary Breast/Ovarian Cancer - BRCA2; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• MTD of veliparib, defined as the highest dose tested in which fewer than 33% of patients experienced dose-limiting toxicity attributable to the study regimen, when at least 6 patients were treated at that dose and were evaluable for toxicity

  Day 21

Secondary Outcomes (4)

• Toxicity profile, defined by the incidence of toxicity, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 30 days post-treatment

• Pharmacokinetic (PK) parameters of veliparib in plasma and urine samples

  Baseline and day 1 of courses 1 and 4

• Pharmacokinetic (PK) parameters of cisplatin in plasma samples

  Baseline and day 1 of courses 1 and 4

• Pharmacodynamic parameters of PARP inhibition

  Baseline and day 1 of courses 1 and 4

Other Outcomes (5)

• Progression-free survival

  The number of days from the date the subject started study drug to the date the subject experiences an event of disease progression, or to the date of death if disease progression is not reached, assessed up to 30 days

• Time to disease progression

  The number of days from the date the subject started study drug to the date of the subject's disease progression, assessed up to 30 days

• Proportion of patients achieving a complete response (CR) or partial response (PR) (objective response rate)

  Up to 30 days

Study Arms (1)

Treatment (veliparib with cisplatin and vinorelbine tartrate)

EXPERIMENTAL

Patients receive veliparib PO BID on days 1-14 (days 0-13 of course 1 only). Patients also receive cisplatin IV over 1 hour on day 1 and vinorelbine ditartrate IV over 10-20 minutes on days 1 and 8. Treatment repeats every 21 days for 6-10 courses in the absence of disease progression or unacceptable toxicity. Treatment with veliparib alone may continue in the absence of disease progression or unacceptable toxicity.

Drug: veliparib; Drug: cisplatin; Drug: vinorelbine tartrate; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

veliparib DRUG

Given PO

Also known as: ABT-888

Treatment (veliparib with cisplatin and vinorelbine tartrate)

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Treatment (veliparib with cisplatin and vinorelbine tartrate)

vinorelbine tartrate DRUG

Given IV

Also known as: Eunades, navelbine ditartrate, NVB, VNB

Treatment (veliparib with cisplatin and vinorelbine tartrate)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (veliparib with cisplatin and vinorelbine tartrate)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (veliparib with cisplatin and vinorelbine tartrate)

Eligibility Criteria

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

You may qualify if:

• Recurrent and/or metastatic breast cancer
• Subjects must meet at least one of the following two criteria:
• Histologically confirmed primary or metastatic site that is estrogen receptor (ER)-negative (less than 10%), progesterone receptor (PR)-negative (less than 10%), and human epidermal growth factor receptor (HER)2 non-over expressing by immunohistochemistry (IHC) (0, 1) or non-amplified by fluorescence in situ hybridization (FISH)
• Confirmed BRCA1 or BRCA2 mutation associated breast cancer
• Subjects must have measurable disease, defined as at least one lesion that can be measured in at least one dimension with a minimum size of: longest diameter \>= 10 mm (computed tomography \[CT\] scan slice thickness no greater than 5 mm); 10 mm caliper measurement by clinical exam; to be considered pathologically enlarged and measurable, a lymph node must be \>= 15 mm in short axis when assessed by CT scan
• Subjects may have had any number of prior chemotherapy, endocrine therapy, immunologic, or biologic regimens for metastatic breast cancer
• Performance status \>= 60% on the Karnofsky scale (Eastern Cooperative Oncology Group \[ECOG\] =\< 2)
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3 (1.5 x 10\^9/L)
• Platelets \>= 100,000/mm\^3 (100 x 10\^9/L)
• Hemoglobin \>= 9.0 g/dL
• Serum creatinine =\< 1.5 x upper normal limit of institution's normal range OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for subjects with creatinine levels above institutional normal
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 2.5 x the upper normal limit of institution's normal range; for subjects with liver metastases, AST and/or ALT \< 5 x the upper normal limit of institution's normal range
• Bilirubin =\< 1.5 x the upper normal limit of institution's normal range; subjects with Gilbert's syndrome may have a bilirubin \> 1.5 x the upper normal limit of institution's normal range
• Partial thromboplastin time (PTT) must be =\< 1.5 x the upper normal limit of institution's normal range and international normalized ratio (INR) \< 1.5; subjects on anticoagulant (such as Coumadin) will have PTT and INR as determined by the investigator
• Women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and for 90 days following completion of therapy; women of childbearing potential must have a negative serum pregnancy test within 21 days prior to initiation of treatment and/or be confirmed as having postmenopausal status; criteria for determining menopause include any of the following: prior bilateral oophorectomy; age \>= 60 years; age \< 60 years and amenorrheic for at least 12 months in the absence of chemotherapy, endocrine therapy, or ovarian suppression and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range;

You may not qualify if:

• Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, biologic or any investigational therapy within either 28 days or 5 half-lives of a targeted therapy (whichever is shorter), prior to study drug administration; subjects receiving hormone therapy, bisphosphonates, denosumab or luteinizing-hormone-releasing hormone (LHRH)-agonists are eligible; subjects who have not recovered to within one grade level (not to exceed grade 2) of their baseline following a significant adverse event or toxicity attributed to prior anti-cancer treatment are excluded
• Subjects with a known hypersensitivity to platinum compounds or vinorelbine
• Subjects with baseline peripheral neuropathy that exceeds grade 1
• Clinically significant and uncontrolled major medical condition(s) including but not limited to:
• Active uncontrolled infection
• Symptomatic congestive heart failure
• Unstable angina pectoris or cardiac arrhythmia
• Psychiatric illness/social situation that would limit compliance with study requirements
• Any medical condition, which in the opinion of the study investigator, places the subject at an unacceptably high risk for toxicities
• Subjects with significant fluid retention, including ascites or pleural effusion, may be allowed at the discretion of the principal investigator
• Subject is pregnant or lactating

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

veliparib; Cisplatin; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Jennifer Specht

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  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 13, 2010
• First Posted: April 15, 2010
• Study Start: July 1, 2010
• Primary Completion: February 1, 2015
• Study Completion: April 1, 2017
• Last Updated: August 10, 2017

Record last verified: 2017-08

Locations

US (1)