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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01123876
Recruitment Status : Completed
First Posted : May 14, 2010
Last Update Posted : January 21, 2015
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )

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

Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: Veliparib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label, Dose-Escalation Study of Veliparib in Combination With Bimonthly FOLFIRI in Subjects With Advanced Solid Tumors
Study Start Date : March 2010
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer
U.S. FDA Resources

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 Name: ABT-888, Veliparib

Primary Outcome Measures :
  1. 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 ]

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

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01123876

United States, Arizona
Site Reference ID/Investigator# 24987
Scottsdale, Arizona, United States, 85258
United States, California
Site Reference ID/Investigator# 24985
Los Angeles, California, United States, 90033
Site Reference ID/Investigator# 26742
Los Angeles, California, United States, 90033
United States, District of Columbia
Site Reference ID/Investigator# 24986
Washington, District of Columbia, United States, 20007
United States, North Carolina
Site Reference ID/Investigator# 24922
Durham, North Carolina, United States, 27710
United States, Tennessee
Site Reference ID/Investigator# 24983
Nashville, Tennessee, United States, 37232-6868
Korea, Republic of
Site Reference ID/Investigator# 75713
Seoul, Korea, Republic of, 138-736
Site Reference ID/Investigator# 75714
Seoul, Korea, Republic of
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Study Director: Stacie Shepherd, MD AbbVie

Responsible Party: AbbVie (prior sponsor, Abbott) Identifier: NCT01123876     History of Changes
Other Study ID Numbers: M10-977
First Posted: May 14, 2010    Key Record Dates
Last Update Posted: January 21, 2015
Last Verified: January 2015

Keywords provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):
Gastric Cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents