Breast CancerPhase 2NCT01009788
ABT-888 and Temozolomide for Metastatic Breast Cancer and BRCA1/2 Breast Cancer
A Phase 2 study testing ABT-888 and temozolomide in people with Breast Cancer and Metastatic Breast Cancer, run by Steven J Isakoff, MD, PhD at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Metastatic Breast Cancer, BRCA1 Gene Mutation
- What is being tested?
- ABT-888 and temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2009to Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
- EXPANSION COHORT:
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase 2 Study of ABT-888 and Temozolomide for Metastatic Breast Cancer and an Expansion Cohort in BRCA1/2 Mutation Carriers
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.
ONLY THE EXPANSION COHORT BELOW IS RECRUITING:
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.
Read the 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.
- Being tested
- ABT-888, temozolomide
- Keywords
- ABT-888, temozolomide, TMZ
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABT-888Drug
Also called veliparib
Capsules (30-40 mg) taken orally twice a day on days 1-7 of each 28 day cycle
temozolomideDrug
Also called TMZ
Capsules (150 mg/m^2 initially, and 200 mg/m^2 starting cycle 2 if tolerated) taken orally once a day on days 1 through 5 of a 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| TMZ/ABT888 Primary Cohort | Experimental | Primary cohort included patients unselected for BRCA1/2 mutations or breast cancer subtype.
Combination therapy with temozolomide and veliparib (28 day cycle) Veliparib 30-40 mg orally twice/day days 1-7 Temozolomide 150 mg/m^2 orally once daily days 1-5, increased to 200 mg/m^2 starting cycle 2 as tolerated Receives: Drug: ABT-888; Drug: temozolomide |
| TMZ/ABT888 Expansion Cohort | Experimental | Expansion cohort included patients with BRCA1/2 deleterious mutations.
Combination therapy with temozolomide and veliparib (28 day cycle) Veliparib 30 mg orally twice/day days 1-7 Temozolomide 150 mg/m^2 orally once daily days 1-5, increased to 200 mg/m^2 starting cycle 2 as tolerated Receives: Drug: ABT-888; Drug: temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) of ABT-888 and Temozolomide (TMZ) in Metastatic Breast Cancer
Objective response rate (ORR) is defined as the percentage of enrolled patients who have a partial or complete response per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 guidelines. A partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A complete response is defined as disappearance of all target lesions, with any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm.
Measured: 2 years
Secondary outcomes (2)
Progression Free Survival
Progression free survival is defined as the length of time from enrollment until disease progression, death, or date of last patient contact. Progressive disease was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progressive disease is defined as at least a 20% increase (at least 5 mm) in the sum of the LD of target lesions in comparison with the lowest sum achieved on study or the appearance of one or more new lesions, and/or unequivocal progression of non-target lesions.
Measured: 5 years
Clinical Benefit Rate
Clinical benefit rate (CBR) is defined as the percentage of patients who achieve a partial or complete response or stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A complete response is defined as disappearance of all target lesions, with any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. Progressive disease is defined as at least a 20% increase (at least 5 mm) in the sum of the LD of target lesions in comparison with the lowest sum achieved on study or the appearance of one or more new lesions, and/or unequivocal progression of non-target lesions.
Measured: Four months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionSep 2012
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steven J Isakoff, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Abbott
- Responsible party
- Sponsor-investigator, Steven J Isakoff, MD, PhD, Massachusetts General Hospital
- Investigators
- Steven Isakoff, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01009788
- Sponsor's protocol ID
- 09-261
- Status last verified
- Feb 2025
- First submitted
- 5 Nov 2009
- Last updated
- 14 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Xu J, Keenan TE, Overmoyer B, Tung NM, Gelman RS, Habin K, Garber JE, Ellisen LW, Winer EP, Goss PE, Yeap BY, Chabner BA, Isakoff SJ. Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations. Breast Cancer Res Treat. 2021 Oct;189(3):641-651. doi: 10.1007/s10549-021-06292-7. Epub 2021 Aug 20.
PubMed 34417675
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of ABT-888 and Temozolomide for Metastatic Breast Cancer and an Expansion Cohort in BRCA1/2 Mutation Carriers
- ClinicalTrials.gov ID
- NCT01009788
- Acronym / sponsor ID
- 09-261
- Keywords
- ABT-888, temozolomide, TMZ
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Steven J Isakoff, MD, PhDUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Abbott
- Study start
- Nov 2009 (actual)
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 9 Nov 2009 (estimated)
- Results
- Posted 14 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
ONLY THE EXPANSION COHORT BELOW IS RECRUITING:
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TMZ/ABT888 Primary Cohort | Experimental | Drug: ABT-888, Drug: temozolomidePrimary cohort included patients unselected for BRCA1/2 mutations or breast cancer subtype. Combination therapy with temozolomide and veliparib (28 day cycle) Veliparib 30-40 mg orally twice/day days 1-7 Temozolomide 150 mg/m^2 orally once daily days 1-5, increased to 200 mg/m^2 starting cycle 2 as tolerated |
| TMZ/ABT888 Expansion Cohort | Experimental | Drug: ABT-888, Drug: temozolomideExpansion cohort included patients with BRCA1/2 deleterious mutations. Combination therapy with temozolomide and veliparib (28 day cycle) Veliparib 30 mg orally twice/day days 1-7 Temozolomide 150 mg/m^2 orally once daily days 1-5, increased to 200 mg/m^2 starting cycle 2 as tolerated |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (16 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABT-888Also: veliparibCapsules (30-40 mg) taken orally twice a day on days 1-7 of each 28 day cycle | Drug | TMZ/ABT888 Expansion Cohort, TMZ/ABT888 Primary Cohort |
| temozolomideAlso: TMZCapsules (150 mg/m^2 initially, and 200 mg/m^2 starting cycle 2 if tolerated) taken orally once a day on days 1 through 5 of a 28 day cycle | Drug | TMZ/ABT888 Expansion Cohort, TMZ/ABT888 Primary Cohort |
Primary outcome
Objective Response Rate (ORR) of ABT-888 and Temozolomide (TMZ) in Metastatic Breast Cancer
Time frame: 2 years
Objective response rate (ORR) is defined as the percentage of enrolled patients who have a partial or complete response per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 guidelines. A partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A complete response is defined as disappearance of all target lesions, with any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm.
2 secondary outcomes
Progression Free Survival
Time frame: 5 years
Clinical Benefit Rate
Time frame: Four months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34417675Xu J, Keenan TE, Overmoyer B, Tung NM, Gelman RS, Habin K, Garber JE, Ellisen LW, Winer EP, Goss PE, Yeap BY, Chabner BA, Isakoff SJ. Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations. Breast Cancer Res Treat. 2021 Oct;189(3):641-651. doi: 10.1007/s10549-021-06292-7. Epub 2021 Aug 20.
- Individual participant dataSharing planned: No
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Isakoff, MD, PhD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ABT-888 and temozolomide in people with Breast Cancer and Metastatic Breast Cancer, run by Steven J Isakoff, MD, PhD at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) of ABT-888 and Temozolomide (TMZ) in Metastatic Breast Cancer (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01009788, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2025.