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

NCT01085422 | Completed Phase 1

• 1 other identifier: M11-070
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Protein-specific antigen (PSA) test

  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 Outcomes (2)

• Assessment of Efficacy

  Day 0 through investigator-determined discontinuation

• Assessment of Safety

  Day 0 through survival follow-up

Study Arms (1)

Arm A

EXPERIMENTAL

Drug: ABT-888; Drug: temozolomide

Interventions

ABT-888 DRUG

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

Also known as: ABT-888, veliparib

Arm A

temozolomide DRUG

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

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead
• Prostate Cancer Clinical Trials Consortium: collaborator

Related Publications (1)

• Hussain M, Carducci MA, Slovin S, Cetnar J, Qian J, McKeegan EM, Refici-Buhr M, Chyla B, Shepherd SP, Giranda VL, Alumkal JJ. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer. Invest New Drugs. 2014 Oct;32(5):904-12. doi: 10.1007/s10637-014-0099-0. Epub 2014 Apr 26.

  PMID: 24764124 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

veliparib; Temozolomide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bhardwaj Desai, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2010
• First Posted: March 11, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: November 21, 2017

Record last verified: 2013-01