Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer

NCT00535119 | Completed Phase 1

• 8 other identifiers: NCI-2009-00258PCI-07-015CDR0000566233UPCI # 07-0157967N01CM00038P30CA047904U01CA099168
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 7

Brief Summary

This phase I trial is studying the side effects and best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with advanced solid cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with carboplatin and paclitaxel may help kill more tumor cells.

Conditions

Adult Solid Neoplasm; BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Hereditary Breast and Ovarian Cancer Syndrome

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose (RP2D) for each stratum

  The RP2D for each cohort will be defined by the study separately. Standard up \& down dose-escalation scheme to determine the RP2D will be use, and toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

  Up to 4 weeks

Secondary Outcomes (7)

• Dose-limiting toxicity (DLT)

  During course 1

• Frequency of platinum-DNA adducts

  At baseline and 4 weeks post-treatment

• Incidence of stable disease (SD)

  Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment

• PAR levels

  Up to 4 weeks post-treatment

• Responses to veliparib in combination with carboplatin and paclitaxel

  Up to 4 weeks post-treatment

Study Arms (1)

Treatment (enzyme inhibitor therapy and chemotherapy)

EXPERIMENTAL

Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study; Drug: Veliparib

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (enzyme inhibitor therapy and chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy and chemotherapy)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (enzyme inhibitor therapy and chemotherapy)

Pharmacological Study OTHER

Correlative studies

Treatment (enzyme inhibitor therapy and chemotherapy)

Veliparib DRUG

Given PO

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Treatment (enzyme inhibitor therapy and chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed advanced solid malignancy
• Patients enrolled in stratum II of the study must have BRCA1/2 mutation (added 04/07/09)
• Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for \> 3 months and must be off steroid treatment prior to study enrollment
• ECOG performance status 0-2
• Life expectancy \> 12 weeks
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 3 weeks since prior radiotherapy

You may not qualify if:

• Known history of allergic reactions to veliparib, carboplatin, or Cremophor-paclitaxel
• Uncontrolled intercurrent illness, including, but not limited to, any of the following:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situations that would preclude compliance with study requirements
• Peripheral neuropathy \> grade 1
• Inability to take oral medications on a continuous basis
• Active seizure or history of seizure disorder
• Evidence of bleeding diathesis
• Received \> 3 prior chemotherapy regimens for advanced stage disease for patients enrolled in stratum I (there is no upper limit on the number of prior regimens for patients enrolled in stratum II) (added 04/07/09)
• Adjuvant chemotherapy administered ≥ 2 years prior to enrollment to the study does not count as a prior chemotherapy regimen
• Other concurrent investigational agents
• Concurrent combination antiretroviral therapy for HIV-positive patients

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Hereditary Breast and Ovarian Cancer Syndrome

Interventions

Carboplatin; Paclitaxel; Taxes; veliparib

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplastic Syndromes, Hereditary; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Suresh Ramalingam

  University of Pittsburgh Cancer Institute (UPCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2007
• First Posted: September 26, 2007
• Study Start: September 1, 2007
• Primary Completion: October 1, 2012
• Last Updated: May 22, 2015

Record last verified: 2015-04

Locations

US (7)