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ABT-888 and Temozolomide for Metastatic Breast Cancer and BRCA1/2 Breast Cancer

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: NCT01009788
Recruitment Status : Active, not recruiting
First Posted : November 9, 2009
Last Update Posted : August 26, 2019
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Information provided by (Responsible Party):
Steven J Isakoff, MD, PhD, Massachusetts General Hospital

Brief Summary:

The purpose of this research study is to find out if the combination of ABT-888 and temozolomide is safe and effective in treating patients with metastatic breast cancer. ABT-888 works by obstructing a DNA enzyme called poly (ADP-ribose) polymerase (PARP) which helps repair cancer cells damaged by chemotherapy. By blocking the PARP enzyme, the cancer cells are unable to repair themselves and as a result die. The other drug in this study is temozolomide. Temozolomide is designed to damage DNA in order to prevent cancer cells from reproducing. Because PARP inhibitors, such as ABT-888, prevent cancer cells from repairing their own DNA, they enhance the potential of chemotherapy therapy like temozolomide to induce cell death. The combination of ABT-888 and temozolomide has been used in a clinical trial for treatment of other cancers and information for this research study suggests that the combination may help to inhibit growth in breast cancer.


BRCA CARRIER EXPANSION COHORT: The purpose of the expansion cohort is to further evaluate the activity and safety of this combination in BRCA mutation carriers with metastatic breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic Breast Cancer BRCA1 Gene Mutation brca2 Gene Mutation Drug: ABT-888 Drug: temozolomide Phase 2

Detailed Description:
  • Each treatment cycle lasts 28 days. Participants will be given a supply of ABT-88 in the form of capsules which they will take twice daily on days 1-7 of each cycle. Temozolomide is also in capsule form and will be taken once daily on days 1-5 of each cycle.
  • Participants will come into the clinic on day 1 of each cycle and will have the following tests and procedures performed: physical examination, vital signs and blood tests.
  • On day 15 of cycles 1 and 2 and day 22 of each cycle, participants will have blood work done.
  • An assessment fo the tumor by CT scan of the participants chest, abdomen and pelvis will be done every 2 cycles.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of ABT-888 and Temozolomide for Metastatic Breast Cancer and an Expansion Cohort in BRCA1/2 Mutation Carriers
Study Start Date : November 2009
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: TMZ/ABT888
Combination therapy with temozolomide and veliparib
Drug: ABT-888
Capsules taken orally twice a day on days 1-7 of each 28 day cycle
Other Name: veliparib

Drug: temozolomide
capsules taken orally once a day on days 1 through 5 of a 28 day cycle
Other Name: TMZ

Primary Outcome Measures :
  1. To determine the objective response rate (ORR) of ABT-888 and temozolomide (TMZ) in metastatic breast cancer. [ Time Frame: 2 years ]
    To determine the percentage of all enrolled patients who have a partial or complete response

  2. To determine Safety and Efficacy in an Expansion Cohort of BRCA1/2 Mutation Carriers. [ Time Frame: 2 years ]
    An expansion cohort of 20 additional patients with BRCA1/2 Deleterious Mutations will be evaluated to further assess safety and efficacy of the combination of ABT888 and Temozolomide in metastatic breast cancer.

Secondary Outcome Measures :
  1. To further characterize the safety and tolerability of ABT-888 and TMZ in patients with metastatic breast cancer. [ Time Frame: 2 years ]
  2. To evaluate progression free survival. [ Time Frame: 5 years ]
    To determine the median time to progression of all patients

  3. To evaluate the clinical benefit rate. [ Time Frame: 2 years ]
    to determine the percentage of patients who achieve a partial or complete response or stable disease

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  • Histologically or cytologically confirmed breast cancer that is metastatic (Stage IV) or locally advanced recurrent breast cancer that is unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
  • Measurable disease by RECIST criteria
  • All immunohistochemical subtypes of breast cancer are eligible. HER2 positive breast cancer must have progressed on prior standard HER2 therapy or have a contraindication to anti-HER2 therapy.
  • Must have at least 1 prior chemotherapy regimen for metastatic disease, with no limit on total number of prior therapies.
  • 18 years of age or older
  • Life expectancy of at least 12 weeks
  • ECOG Performance Status of 0, 1, or 2
  • Normal organ and marrow function as outlined in the protocol
  • Archived tissue block or 25 unstained slides (from primary and/or metastatic tumor) if available for correlative exploratory studies. Absence of available tissue will not exclude the subjects from participating.
  • CNS metastases are allowed if they are clinically stable without current evidence of symptomatic progression and do not require steroids, whole brain radiation therapy, or stereotactic radiosurgery. This may include brain metastases not previously treated if they are clinically stable as described above.
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
  • Women of child-bearing potential must have a negative pregnancy test within 14 days of registration.
  • Patients must be progressing on their current therapy
  • Prior exposure to single agent PARP inhibitor is allowed, but no prior exposure to PARP with a combination of chemotherapy is allowed.

Exclusion Criteria:

  • Participants who have had chemotherapy, biologic therapy, small molecule targeted therapy or radiotherapy within 14 days prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Anti-cancer hormonal therapy must be stopped 24 hours prior to starting study treatment.
  • Participants may not be receiving any other investigational agents.
  • Prior therapy with TMZ is allowed except if participant has a history of allergic reactions attributed to TMZ, or if therapy was discontinued due to intolerance of or toxicity from TMZ.
  • Leptomeningeal disease
  • CNS involvement requiring steroids (except for patients who recently completed brain radiation and are on stable or tapering doses of steroids).
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, recent myocardial infarction, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, or other comorbid condition that investigator believes may compromise participant's safe and effective participation in the trial.
  • Concurrent radiation therapy is not permitted while on study
  • Concurrent anti-cancer therapy is not permitted on study
  • Pregnant and breast feeding women
  • History of uncontrolled seizure disorder
  • Individuals with a history of other malignancies are eligible if they meet the following criteria: a) the other malignancy was treated with curative intent and is deemed by the investigator to be at low risk of recurrence , AND b) a metastatic lesion has been histologically confirmed as breast cancer, c) individuals with the following cancers are eligible if diagnosed and treated: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.


An expansion cohort will have the same eligibility requirements with the following notable exceptions:

  • Patients must have known deleterious mutation of BRCA1/2
  • Prior PARP inhibitor combinations with chemotherapy are allowed
  • Any number of prior therapies is allowed, including first line

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): NCT01009788

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Steven J Isakoff, MD, PhD
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
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Principal Investigator: Steven Isakoff, MD, PhD Massachusetts General Hospital
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Responsible Party: Steven J Isakoff, MD, PhD, Attending Physician, Massachusetts General Hospital Identifier: NCT01009788    
Other Study ID Numbers: 09-261
First Posted: November 9, 2009    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Steven J Isakoff, MD, PhD, Massachusetts General Hospital:
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors