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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01104259
First received: April 13, 2010
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: veliparib
Drug: cisplatin
Drug: vinorelbine tartrate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of ABT-888 in Combination With Cisplatin and Vinorelbine for Patients With Advanced Triple Negative Breast Cancer and/or BRCA-Mutation Associated Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 21 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity profile, defined by the incidence of toxicity, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic (PK) parameters of veliparib in plasma and urine samples [ Time Frame: Baseline and day 1 of courses 1 and 4 ] [ Designated as safety issue: No ]
    The PK parameters determined will be: AUC0-t (the area under the concentration-time curve over a dosing interval), Cmax (maximal concentration), Tmax (time to maximal concentration), Vd (volume of distribution), CL/F (oral clearance for veliparib), CL (clearance for cisplatin), and t1/2 (elimination half-life). To improve understanding of systemic bioavailability, the amount of veliparib excreted in the urine for each collection interval will be calculated by the product of urinary drug concentration and urine volume.

  • Pharmacokinetic (PK) parameters of cisplatin in plasma samples [ Time Frame: Baseline and day 1 of courses 1 and 4 ] [ Designated as safety issue: No ]
    The PK parameters determined will be: AUC0-t, Cmax, Tmax, Vd, CL/F, CL, and t1/2 .

  • Pharmacodynamic parameters of PARP inhibition [ Time Frame: Baseline and day 1 of courses 1 and 4 ] [ Designated as safety issue: No ]
    Assessed by measuring changes in PAR levels in peripheral blood mononuclear cells and in tumor tissue (if available).


Other Outcome Measures:
  • Progression-free survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier methodology and 95% confidence interval.

  • Time to disease progression [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier methodology and 95% confidence interval.

  • Proportion of patients achieving a complete response (CR) or partial response (PR) (objective response rate) [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 and estimated with 95% confidence interval.

  • Duration of overall response [ Time Frame: The number of days from the day the criteria are met for CR or PR (whichever is recorded first) to the date that progressive disease is objectively documented, assessed up to 30 days ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier Methodology.

  • ECOG performance status [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Descriptive statistics will be summarized for each assessment.


Estimated Enrollment: 56
Study Start Date: July 2010
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (veliparib with cisplatin and vinorelbine tartrate)
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
Given PO
Other Name: ABT-888
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: vinorelbine tartrate
Given IV
Other Names:
  • Eunades
  • navelbine ditartrate
  • NVB
  • VNB
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of ABT-888 (veliparib) when administered daily for 14 days out of a 21 day cycle in combination with cisplatin and vinorelbine (vinorelbine ditartrate) in subjects with metastatic triple negative breast cancer (TNBC) and breast cancer (BRCA) mutation associated breast cancer.

SECONDARY OBJECTIVES:

I. Assess the pharmacokinetic profile of ABT-888 when combined with cisplatin and vinorelbine and the safety/tolerability profile of the combination.

II. Evaluate the level of poly ADP ribose polymerase (PARP) inhibition at each dose level to determine whether maximal PARP inhibition is achieved.

III. Identify the subgroup of triple negative breast cancer patients who will potentially derive the most benefits from PARP inhibition combined with platinum-based chemotherapy.

OUTLINE: This is a dose-escalation study of veliparib.

Patients receive veliparib orally (PO) twice daily (BID) on days 1-14 (days 0-13 of course 1 only). Patients also receive cisplatin intravenously (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.

After completion of study treatment, patients are followed for up to 30 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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;

    • Total abstinence from sexual intercourse (minimum one complete menstrual cycle)
    • Vasectomized partner of female subjects
    • Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
    • Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
    • Intra-uterine device (IUD)
  • Male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completion of therapy
  • Radiation therapy of a non-target lesion must have been completed at least 2 weeks prior to the enrollment date
  • Subjects with known brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 14 days of stable neurologic function prior to the first dose of study drug
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01104259

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Jennifer Specht Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01104259     History of Changes
Other Study ID Numbers: 7161, NCI-2010-00356, P30CA015704, 7161, P30CA015704
Study First Received: April 13, 2010
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Neoplasms, Male
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Breast Diseases
Skin Diseases
Vinorelbine
Cisplatin
Vinblastine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2014