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A Phase 2 Study of ABT-888 and Temozolomide for Metastatic Breast Cancer and an Expansion Cohort in BRCA1/2 Mutation Carriers

Phase 2
18 Years
Open (Enrolling)
Breast Cancer, Metastatic Breast Cancer, BRCA1 or BRCA2 Associated Breast Cancer

Thank you

Trial Information

A Phase 2 Study of ABT-888 and Temozolomide for Metastatic Breast Cancer and an Expansion Cohort in BRCA1/2 Mutation Carriers

- 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

- 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

- On day 15 of cycles 1 and 2 and day 22 of each cycle, participants will have blood work

- An assessment fo the tumor by CT scan of the participants chest, abdomen and pelvis
will be done every 2 cycles.

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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the objective response rate (ORR) of ABT-888 and temozolomide (TMZ) in metastatic breast cancer.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Steven Isakoff, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

November 2009

Completion Date:

December 2014

Related Keywords:

  • Breast Cancer
  • Metastatic Breast Cancer
  • BRCA1 or BRCA2 Associated Breast Cancer
  • ABT-888
  • temozolomide
  • TMZ
  • Breast Neoplasms



Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Massachusetts General HospitalBoston, Massachusetts  02114-2617