A Study Combining ABT-888, Oral PARP Inhibitor, With Temozolomide in Patients With Metastatic Prostate Cancer

November 17, 2017 updated by: AbbVie (prior sponsor, Abbott)

A Pilot Study Combining ABT-888, an Oral PARP Inhibitor, With Temozolomide in Patients With Metastatic Castration Resistant Prostate Cancer Who Have Failed Up to Two Non-hormonal Systemic Therapies

Assess whether the combination of ABT-888 with temozolomide (TMZ) has activity in subjects with metastatic castration resistant prostate cancer (CRPC) as reflected by the prostate-specific antigen (PSA) response.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Subject has histologically or cytologically confirmed prostate cancer.
  • Metastatic prostate cancer with measurable and/or bony disease that has progressed despite androgen deprivation therapy and at least one and no more than two prior systemic non hormonal therapies (at least one must include docetaxel) for castration resistant metastatic disease.
  • At least 28 days must have elapsed since completion of prior anti-cancer therapy and must have recovered from all side effects to < Grade 1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. ECOG PS 3 is allowed if due to pain.

  • Subjects must have PSA progression defined as:

    • A 25% increase in PSA over a baseline value with an increase in the absolute value of PSA level by 2 ng/ml, that is confirmed by another PSA level at a minimum of 1 week interval.
  • Subjects must have a minimum PSA of > 2 ng/ml.
  • Testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy.
  • No investigational or commercial agents (other than LHRH analogue) or therapies including other hormonal agents such as antiandrogens or herbal medications may be administered with the intent to treat the subject's malignancy. Subjects on stable doses of steroids or megestrol acetate (for hot flashes or appetite) are allowed.
  • Four weeks must have elapsed since major surgery.
  • Prior radiotherapy is allowed as long as the bone marrow function is adequate and at least 4 weeks has elapsed since completion of radiation therapy. No prior radiopharmaceuticals are allowed.

  • Subjects must have normal organ and bone marrow function as defined below obtained within two weeks from treatment initiation:

    • Bone Marrow: absolute neutrophil count ≥ 1,500/mcL; platelets ≥ 100,000/mcL; hemoglobin ≥ 9.0 g/dL
    • Renal function: Serum creatinine ≤ 1.5 × upper limits of institution's normal (ULIN) range or creatinine clearance ≥ 50 mL/min/1.73 m2
    • Hepatic Function: Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) ≤ 2.5 × ULIN. For subjects with liver metastases, AST and/or ALT < 5 × ULIN. Bilirubin ≤ 1.5 × ULIN (Subjects with Gilbert's Syndrome may have a bilirubin ≥ 1.5 × ULIN)
  • Subjects who refuse to provide blood samples for the correlative studies will be eligible.
  • ABT-888 and temozolomide are known to be teratogenic, therefore men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Subjects with treated and controlled epidural disease are permitted into the study.
  • 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.

Exclusion Criteria:

  • A subject with cord compression or a history of uncontrolled central nervous system (CNS) metastases or leptomeningeal disease.
  • Subject has had prior therapies with Dacarbazine (DTIC) or TMZ containing regimens.
  • The subject has received an investigational agent within 28 days prior to study drug administration.
  • Subject with a history of seizure disorder and currently receiving medications for seizure disorders (e.g., steroid or anticonvulsant drugs).
  • The subject has had another active malignancy within the past 1 year with the exception of definitely treated carcinomas in situ, superficial bladder cancer, and non-melanoma carcinoma of the skin. Questions regarding inclusion of individual subjects should be discussed with the Abbott Medical Monitor.

  • Clinically significant and uncontrolled major medical condition(s) 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,
    • Or any medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities.
  • Subject has previously been treated with a PARP inhibitor.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm A
Drug: ABT-888
Subjects will be given ABT-888 on Days 1 -7 every 28 days orally and temozolomide on days 1-5 on days 1-5 every 28 days orally with ABT-888
Other Names:
  • ABT-888, veliparib
Drug: temozolomide
Subjects will be given ABT-888 40 mg twice daily on Days 1 -7 every 28 days orally and temozolomide on days 1-5 every 28 days orally with ABT-888

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Protein-specific antigen (PSA) test
Time Frame: Day 0 through investigator-determined discontinuation (final visit)
This is performed to assess if ABT-888 combined with temozolomide has activity in patients with prostate cancer as reflected by the prostate-specific antigen (PSA).
Day 0 through investigator-determined discontinuation (final visit)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of Efficacy
Time Frame: Day 0 through investigator-determined discontinuation
Evaluate the safety and tolerability of the combination therapy through safety assessments (i.e. electrocardiogram (ECG), clinical laboratory tests, vital signs, Adverse Event assessments, serious adverse events, physical exams, computed tomography (CT) scans)
Day 0 through investigator-determined discontinuation
Assessment of Safety
Time Frame: Day 0 through survival follow-up
Assess the objective response rate (ORR), PSA decline, time to progression (TTP), progression free survival (PFS), and overall survival (OS)
Day 0 through survival follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie (prior sponsor, Abbott)

Collaborators

Prostate Cancer Clinical Trials Consortium

Investigators

  • Study Director: Bhardwaj Desai, MD, AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (ACTUAL)

June 1, 2011

Study Completion (ACTUAL)

June 1, 2011

Study Registration Dates

First Submitted

March 10, 2010

First Submitted That Met QC Criteria

March 10, 2010

First Posted (ESTIMATE)

March 11, 2010

Study Record Updates

Last Update Posted (ACTUAL)

November 21, 2017

Last Update Submitted That Met QC Criteria

November 17, 2017

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M11-070

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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