Evaluating the Safety and Tolerability of the Poly-ADP Ribose (PARP) Inhibitor With FOLFIRI in Subjects With Solid Tumor

July 29, 2021 updated by: AbbVie (prior sponsor, Abbott)

A Phase 1 Open-Label, Dose-Escalation Study of Veliparib in Combination With Bimonthly FOLFIRI in Subjects With Advanced Solid Tumors

Assess whether the combination of ABT-888 with FOLFIRI has activity in subjects with gastric cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 138-736
        • Site Reference ID/Investigator# 75713
      • Seoul, Korea, Republic of
        • Site Reference ID/Investigator# 75714
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Site Reference ID/Investigator# 24987
    • California
      • Los Angeles, California, United States, 90033
        • Site Reference ID/Investigator# 24985
      • Los Angeles, California, United States, 90033
        • Site Reference ID/Investigator# 26742
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Site Reference ID/Investigator# 24986
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Site Reference ID/Investigator# 24922
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6868
        • Site Reference ID/Investigator# 24983

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Subject must be at least 18 years of age.
  2. Subjects in the dose escalation cohorts must have: * Subjects with histologically or cytologically confirmed malignancy that is meta static or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective or for whom treatment with FOLFIRI is a viable option.
  3. Subjects in the expanded safety cohort must have: * Histological confirmed advanced colorectal cancer.
  4. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.
  5. Subject must have adequate hematologic, renal and hepatic function as follows: * Bone Marrow: Absolute neutrophil count ANC >= 1,500/mm3; Platelets >= 100,000/mm3; Hemoglobin >= 9.5 g/dL; * Renal function: Serum creatinine < 1.5 * upper normal limit of institution's normal range OR creatinine clearance <= 50 mL/min/1.73m2 for subjects with creatinine levels above institutional normal; * Hepatic function: AST and ALT <= 2.5 * the upper normal limit of institution's normal range. For subjects with liver metastases, AST and ALT <= 5 * the upper normal limit of institution's normal range; * Bilirubin <= 1.5 * the upper normal limit of institution's normal range;
  6. Partial Thromboplastin Time (PTT) must be <= 1.5 * the upper normal limit of institution's normal range and INR < 1.5. Subjects on anticoagulant (such as Coumadin) will have PTT and INR as determined by the investigator.
  7. 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 post menopausal women must be amenorrheic for at least 12 months to be considered of non childbearing potential. * 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); * IUD (Intra-Uterine Device); * Additionally, 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 completions of therapy.
  8. Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
  9. The subject has received up to 3 prior DNA damaging agents or cytotoxic chemotherapy treatments (prior therapies with biologic agents including, IL -2, interferon, vaccines, immunostimulants and signal transduction inhibitors are allowed) Chemotherapy received as adjuvant therapy before 2 years will not be considered as prior chemotherapy.

Exclusion Criteria:

  1. Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within 28 days prior to study drug administration. Subjects receiving hormone therapy, bisphosphonates or 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 previously anti-cancer treatment are excluded.
  2. Subjects in the expanded safety cohorts only, have previously been treated with a PARP inhibitor.
  3. Subjects with a known history of brain metastases and primary CNS tumors
  4. Subjects with a known hypersensitivity to CPT11, 5-FU or Folinic Acid.
  5. Clinically significant and uncontrolled major medical condition(s) including but not limited to: * Uncontrolled nausea/vomiting/diarrhea; * Active uncontrolled infection; * Symptomatic congestive heart failure; * Unstable angina pectoris or cardiac arrhythmia; * Psychiatric illness/social situation that would limit compliance with study requirements. * Gilbert's Syndrome * Any medical condition, which in the opinion of the study investigator, places the patient at an unacceptably high risk for toxicities
  6. Subjects that are being treated with Ketoconazole, enzyme-inducing anticonvulsants, and or St. John's Wort.
  7. Subject is pregnant or lactating.
  8. Subject who requires parenteral nutrition, tube feeding or has evidence of partial bowel obstruction or perforation within 28 days prior to study drug administration.
  9. The subject has had another active malignancy within the past 3 years except for any cancer in situ that the Principal Investigator considers to be cured.
  10. Previous exposure to Irinotecan.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Veliparib and FOLFIRI
Veliparib in combination with FOLFIRI regimen.
Drug: Veliparib
Subjects will be given Veliparib twice daily on Days 1-5 and 15-19 every 28 days orally
Other Names:
  • ABT-888, Veliparib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the MTD and establish the recommended phase 2 dose of Veliparib in combination with two different FOLFIRI regimens that include a reduced regimen (150 mg/m2 irinotecan) and the standard regimen (180 mg/m2) in subjects with advanced solid tumors
Time Frame: Screening to follow up visit
Screening to follow up visit

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess the safety and tolerability, pharmacokinetic profile of the combination at each of the FOLFIRI regimens.
Time Frame: Screening to follow up visit
Screening to follow up visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie (prior sponsor, Abbott)

Investigators

  • Study Director: Stacie Shepherd, MD, AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

April 9, 2010

First Submitted That Met QC Criteria

May 13, 2010

First Posted (Estimate)

May 14, 2010

Study Record Updates

Last Update Posted (Actual)

August 2, 2021

Last Update Submitted That Met QC Criteria

July 29, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M10-977

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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