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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

Phase 1
18 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

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

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

- 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

- 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

- 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

- 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.

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:

Protein-specific antigen (PSA) test

Outcome Description:

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).

Outcome Time Frame:

Day 0 through investigator-determined discontinuation (final visit)

Safety Issue:


Principal Investigator

Bhardwaj Desai, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

April 2010

Completion Date:

June 2011

Related Keywords:

  • Prostate Cancer
  • Prostate Cancer
  • Prostatic Neoplasms



Site Reference ID/Investigator# 25982 Baltimore, Maryland  21231-1000
Site Reference ID/Investigator# 26202 Ann Arbor, Michigan  48109-5946
Site Reference ID/Investigator# 27324 New York, New York  10065
Site Reference ID/Investigator# 27322 Portland, Oregon  97239
Site Reference ID/Investigator# 27323 Madison, Wisconsin  53705