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Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

Primary Purpose

Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
gemcitabine hydrochloride
veliparib
diagnostic laboratory biomarker analysis
pharmacological study
cisplatin
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Adult Primary Liver Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed advanced biliary/pancreatic cancer, urothelial cancer, or non-small cell lung cancer that is metastatic or unresectable
  • Patients with known CNS metastases should be excluded from this clinical trial
  • ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  • Life expectancy of greater than 12 weeks
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST/ALT ≤ 2.5 times institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min
  • QTc interval on ECG ≤ 0.48 seconds by Bazett's calculation (≤ CTCAE v.4 grade 2)
  • Not pregnant or nursing
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • Patients must be able to swallow pills and have no significant impairment in gastrointestinal absorption

  • Patients with known or suspected germline mutation in BRCA1 or BRCA2 are eligible to participate

    • Patients in study screening (primarily those with pancreatic cancer) who have a family history that is suspicious for BRCA1 or BRCA2 germline mutation should be assessed by the BRCAPRO computer program to quantitate the likelihood of harboring a deleterious BRCA mutation
    • Patients found to have a BRCAPRO probability score of ≥ 20% should undergo formal full-sequence BRCA testing
    • Patients in screening with a BRCAPRO probability of ≥ 20% who decline genetic testing are not eligible to participate in this trial due to the potential to confound safety assessment

  • No uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • HIV-positive patients are eligible
  • No active seizure or history of seizure disorder
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib (ABT-888) or other agents used in this study
  • No peripheral neuropathy greater than grade1
  • No prior systemic treatment
  • No prior cytotoxic chemotherapy (neoadjuvant, adjuvant, or metastatic setting)
  • At least 4 weeks since major surgery or radiation therapy
  • Patients may not be receiving any other investigational agents

Sites / Locations

  • Dana-Farber Cancer Institute
  • Penn State Milton S Hershey Medical Center
  • University of Pittsburgh

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (veliparib, gemcitabine hydrochloride, cisplatin)

Arm Description

Patients receive veliparib orally every 12 hours on days 1-12, gemcitabine hydrochloride IV over 30 minutes on days 3 and 10, and cisplatin IV over 60-120 minutes on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with suspected or known germline BRCA mutations may continue to receive single-agent veliparib continuously in the absence of disease progression or unacceptable toxicity. Patients may undergo blood, tumor tissue, and hair follicle sample collection periodically for pharmacokinetic and correlative studies.

Outcomes

Primary Outcome Measures

Maximum-tolerated dose of veliparib in combination with cisplatin and gemcitabine
The maximum toxicity for each category of interest that are determined to be possibly, probably or definitely related to study treatment will be recorded for each patient and the summary results will be tabulated (according to CTCAE v4.0).

Secondary Outcome Measures

Dose-limiting and other toxicities according to CTCAE v4.0
Recommended phase II dose

Full Information

First Posted
January 22, 2011
Last Updated
July 1, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01282333
Brief Title
Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer
Official Title
Phase I Study of Veliparib (ABT-888) in Combination With Cisplatin Plus Gemcitabine in Advanced Biliary, Pancreatic, Urothelial, and Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Terminated
Study Start Date
January 2011 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase I clinical trial is studying the side effects and best dose of veliparib and gemcitabine hydrochloride when given with cisplatin in treating patients with advanced biliary, pancreatic, urothelial, or non-small cell lung 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 cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Veliparib may help cisplatin and gemcitabine hydrochloride work better by making tumor cells more sensitive to the drugs.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum-tolerated dose of veliparib (ABT-888) (days 1-12 of a 21-day schedule) in combination with cisplatin (day 3) and gemcitabine (days 3, 10) in patients with advanced, previously untreated carcinoma of the bile ducts, gallbladder or pancreas, non-small cell lung cancer, or transitional cell carcinoma of the bladder/urothelial tract. SECONDARY OBJECTIVES: I. Describe the dose-limiting toxicity (DLT) and other toxicities associated with veliparib in combination with cisplatin plus gemcitabine as assessed by CTCAE v4.0. II. Determine the recommended phase 2 dose of veliparib (ABT-888) (RP2D) in combination with cisplatin plus gemcitabine. III. Document anti-tumor activity of veliparib (ABT-888), cisplatin, and gemcitabine as assessed by RECIST 1.1. IV. Determine the plasma pharmacokinetics of veliparib (ABT-888), cisplatin, and gemcitabine. V. Determine the abundance of gemcitabine triphosphate in PBMCs following gemcitabine administration. VI. Measure the abundance of DNA-platinum adducts in tumor tissue following cisplatin administration. VII. Measure PARP enzymatic activity in PBMC and tumor tissue following study treatment. VIII. Perform an exploratory correlation between abundance of BRCA and other proteins assessed by tumor immunohistochemistry and clinical response. OUTLINE: This is a multicenter, dose-escalation study of veliparib and gemcitabine hydrochloride. Patients are stratified according to presence of suspected or known BRCA mutations (no vs yes). Patients receive veliparib orally every 12 hours on days 1-12, gemcitabine hydrochloride IV over 30 minutes on days 3 and 10, and cisplatin IV over 60-120 minutes on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with suspected or known germline BRCA mutations may continue to receive single-agent veliparib continuously in the absence of disease progression or unacceptable toxicity. Patients may undergo blood, tumor tissue, and hair follicle sample collection periodically for pharmacokinetic and correlative studies. After completion of study treatment, patients are followed up for 4 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Regional Transitional Cell Cancer of the Renal Pelvis and Ureter, Stage III Bladder Cancer, Stage III Pancreatic Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Bladder Cancer, Stage IV Non-small Cell Lung Cancer, Stage IV Pancreatic Cancer, Transitional Cell Carcinoma of the Bladder, Unresectable Extrahepatic Bile Duct Cancer, Unresectable Gallbladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (veliparib, gemcitabine hydrochloride, cisplatin)
Arm Type
Experimental
Arm Description
Patients receive veliparib orally every 12 hours on days 1-12, gemcitabine hydrochloride IV over 30 minutes on days 3 and 10, and cisplatin IV over 60-120 minutes on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with suspected or known germline BRCA mutations may continue to receive single-agent veliparib continuously in the absence of disease progression or unacceptable toxicity. Patients may undergo blood, tumor tissue, and hair follicle sample collection periodically for pharmacokinetic and correlative studies.
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Other Intervention Name(s)
dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
veliparib
Other Intervention Name(s)
ABT-888
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
diagnostic laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Maximum-tolerated dose of veliparib in combination with cisplatin and gemcitabine
Description
The maximum toxicity for each category of interest that are determined to be possibly, probably or definitely related to study treatment will be recorded for each patient and the summary results will be tabulated (according to CTCAE v4.0).
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Dose-limiting and other toxicities according to CTCAE v4.0
Time Frame
Up to 4 weeks post-treatment
Title
Recommended phase II dose
Time Frame
Up to 4 weeks post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed advanced biliary/pancreatic cancer, urothelial cancer, or non-small cell lung cancer that is metastatic or unresectable Patients with known CNS metastases should be excluded from this clinical trial ECOG performance status ≤ 2 (Karnofsky ≥ 60%) Life expectancy of greater than 12 weeks Absolute neutrophil count ≥ 1,500/mcL Platelets ≥ 100,000/mcL Total bilirubin within normal institutional limits AST/ALT ≤ 2.5 times institutional upper limit of normal Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min QTc interval on ECG ≤ 0.48 seconds by Bazett's calculation (≤ CTCAE v.4 grade 2) Not pregnant or nursing Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation Patients must be able to swallow pills and have no significant impairment in gastrointestinal absorption Patients with known or suspected germline mutation in BRCA1 or BRCA2 are eligible to participate Patients in study screening (primarily those with pancreatic cancer) who have a family history that is suspicious for BRCA1 or BRCA2 germline mutation should be assessed by the BRCAPRO computer program to quantitate the likelihood of harboring a deleterious BRCA mutation Patients found to have a BRCAPRO probability score of ≥ 20% should undergo formal full-sequence BRCA testing Patients in screening with a BRCAPRO probability of ≥ 20% who decline genetic testing are not eligible to participate in this trial due to the potential to confound safety assessment No uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness/social situations that would limit compliance with study requirements HIV-positive patients are eligible No active seizure or history of seizure disorder No history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib (ABT-888) or other agents used in this study No peripheral neuropathy greater than grade1 No prior systemic treatment No prior cytotoxic chemotherapy (neoadjuvant, adjuvant, or metastatic setting) At least 4 weeks since major surgery or radiation therapy Patients may not be receiving any other investigational agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leonard Appleman
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Penn State Milton S Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States

12. IPD Sharing Statement

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Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

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