A Study of ABT-888 in Combination With Temozolomide for Colorectal Cancer

NCT01051596 | Completed Phase 2 Results DMC

• 1 other identifier: 2009-170
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

People with colorectal cancer that cannot be cured by surgery are being asked to participate in this study. The purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and temozolomide for patients with colorectal cancer. Temozolomide acts by damaging deoxyribonucleic acid (DNA) in rapidly dividing cells, in other words, cancer cells. ABT-888 inhibits an enzyme called "PARP" which helps to fix damaged DNA. By inhibiting this enzyme, ABT-888 prevents cancer cells from repairing the damage caused by the temozolomide, and will hopefully increase the killing of cancer cells, and decrease the tumors in the body. ABT-888 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in colorectal cancer. This study will help find out what effects (good and bad) the combination of drugs, temozolomide and ABT-888 has on colorectal cancer. This research is being done because it is not known if ABT-888 will increase the effectiveness of temozolomide for colorectal cancer.

Conditions

Colorectal Cancer

Keywords

metastatic; colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Percent of Patients With Disease Control

  Disease control rate defined as stable disease, partial response, or complete response according to the Response Evaluation Criteria in Solid Tumors (RECIST).

  2 months

Secondary Outcomes (3)

• Median Progression-free Survival Time

  1 year

• Overall Survival

  1 year

• Percent of Patients With an Objective Response

  2 months

Study Arms (1)

ABT-888 and temozolomide

EXPERIMENTAL

Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle

Drug: Temozolomide; Drug: ABT-888

Interventions

Temozolomide DRUG

150mg/m2 Days 1-5 of each 28 day cycle

Also known as: Temodar

ABT-888 and temozolomide

ABT-888 DRUG

40mg orally BID Days 1-7 of each 28 day cycle

Also known as: Veliparib

ABT-888 and temozolomide

Eligibility Criteria

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

You may qualify if:

• Histologically proven colorectal cancer with measurable or evaluable disease
• Progression on or intolerance of or ineligibility for all standard therapies (including regimens containing fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and an anti-EGFR antibody (where appropriate))
• Age \> = 18 years
• ECOG performance status 0-2
• Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intercranial disease and have not had treatment with steroids within 1 week of study enrollment
• At least 21 days since prior anti-cancer therapy, including chemotherapy, biological therapy, radiation therapy or any investigational agent within 4 weeks before starting ABT-888 and temozolomide
• Adequate hepatic, bone marrow, and renal function
• Partial thromboplastin time (PTT) must be \</= 1.5 x the upper limit of institution's normal range and INR \< 1.5. Subjects on anticoagulant will have PTT and INR as determined by the investigator.
• Subject's with significant fluid retention, including ascites or pleural effusion, may be allowed at the discretion of the PI
• Life expectancy \> 12 weeks
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• 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 the IRB prior to the initiation of any screening or study-specific procedures.

You may not qualify if:

• Active severe infection or known chronic infection with HIV, hepatitis B virus, or hepatitis C virus
• Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, myocardial infarction, stroke or congestive heart failure within the last 6 months
• Life threatening visceral disease or other severe concurrent disease
• Women who are pregnant or breastfeeding
• Anticipated patient survival under 3 months
• The subject has had another active malignancy within the past five years except for cervical cancer in site, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
• Clinically significant and uncontrolled major medical conditions 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

Sponsors & Collaborators

• Georgetown University: lead
• Abbott: collaborator

Study Sites (1)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20008, United States

Location

Related Publications (1)

• Pishvaian MJ, Slack RS, Jiang W, He AR, Hwang JJ, Hankin A, Dorsch-Vogel K, Kukadiya D, Weiner LM, Marshall JL, Brody JR. A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients with heavily pretreated metastatic colorectal cancer. Cancer. 2018 Jun 1;124(11):2337-2346. doi: 10.1002/cncr.31309. Epub 2018 Mar 26.

  PMID: 29579325 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Temozolomide; veliparib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Michael Pishvaian, MD, PhD
• Organization: Georgetown University

pishvaim@georgetown.edu

202-444-2223

Study Officials

• Michael J Pishvaian, MD, PhD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 8, 2010
• First Posted: January 18, 2010
• Study Start: September 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 2, 2019
• Results First Posted: April 2, 2019

Record last verified: 2019-03

Locations

US (1)