A Phase I Study of ABT-888 in Combination With Temozolomide in Cancer Patients

NCT ID: NCT00526617

Last Updated: 2017-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-08-31

Brief Summary

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This Phase I clinical trial is studying the side effects and best dose of ABT-888 when given together with Temozolomide (chemotherapy) in treating patients with solid tumors, including metastatic melanoma (MM), BRCA deficient breast, ovarian, primary peritoneal, or fallopian tube cancer, and hepatocellular carcinoma (HCC).

Detailed Description

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A Phase 1, multicenter, dose-escalation study evaluating the safety and tolerability of the PARP inhibitor ABT-888 in combination with Temozolomide (TMZ) in subjects with non-hematologic malignancies (NHM), including metastatic melanoma (MM), BRCA deficient breast, ovarian, primary peritoneal, or fallopian tube cancer, and hepatocellular carcinoma (HCC).

Conditions

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Non-hematologic Malignancies Metastatic Melanoma Breast Cancer Ovarian Cancer Primary Peritoneal Cancer Fallopian Tube Cancer Hepatocellular Carcinoma

Keywords

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Solid Tumor Melanoma Breast cancer Ovarian cancer Primary peritoneal cancer Fallopian tube cancer Hepatocellular carcinoma HCC BRCA deficient BRCA mutation Temozolomide Temodar TMZ ABT-888 PARP inhibitor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Open Label

Within each dose level, subjects are treated with the same regimen/doses of ABT-888 and TMZ.

Group Type EXPERIMENTAL

ABT-888

Intervention Type DRUG

Oral capsules

Temozolomide

Intervention Type DRUG

Oral capsules

Interventions

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ABT-888

Oral capsules

Intervention Type DRUG

Temozolomide

Oral capsules

Intervention Type DRUG

Other Intervention Names

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Temodar TMZ

Eligibility Criteria

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Inclusion Criteria

Dose escalation and expanded safety cohorts

* Evaluable disease, histologically confirmed malignancy (metastatic or unresectable) and standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective
* ECOG Performance Score less than or equal to 2
* Adequate hematologic, renal and hepatic function
* Normal sodium, calcium and magnesium levels
* Voluntarily signed informed consent

Expanded Safety Cohorts Only

* Population:
* Metastatic melanoma (MM)
* Hepatocellular carcinoma (HCC) Child Pugh Category A and B classification only
* BRCA deficient tumor status\*: advanced breast cancer (with soft tissue disease), or advanced ovarian cancer, or advanced primary peritoneal cancer, or advanced fallopian tube cancer\*

\*Patients must have histologically or cytologically confirmed solid tumors with a positive genetic test result documenting BRCA 1 or BRCA 2 mutation status, to be considered eligible.
* Serial tumor biopsies: Required for all subjects enrolled in one of the Expanded Low Dose Safety Cohorts.

Exclusion Criteria

Dose Escalation and Expanded Safety Cohorts

* Known central nervous system (CNS) metastases or CNS primary cancer.
* Previous or current malignancies at other sites, except: adequately treated in situ carcinoma of cervix uteri; basal/squamous cell carcinoma of skin; previous malignancy considered cured.
* Previous history or current seizure disorder.
* Clinically significant and uncontrolled major medical condition(s) or any medical condition that places the subject at an unacceptably high risk for toxicities.
* Transplant recipients and patients receiving combination anti-retroviral therapy for HIV due to the use of immunosuppressant therapies.
* Lactating or pregnant female.
* Chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy will not be allowed within either 4 weeks, or 5 half lives of a targeted therapy prior to study drug administration (Study Day 1).
* Prior therapy with regimens containing dacarbazine (DTIC) or TMZ is not permitted.
* Anti-cancer therapy is not permitted during the treatment portion of the study.
* Hormone therapy, bisphosphonates or LHRH-agonists for prostate cancer are permitted prior to and during the study.
* Significant adverse event or toxicity due to previous anti-cancer treatment that has not recovered to within one grade level (not to exceed Grade 2) of baseline.

Expanded Safety Cohorts Only:

* MM Only: Prior treatment with DNA damaging agents or cytotoxic chemotherapy including carboplatin, cisplatin, fotemustine, paclitaxel, vincristine, TMZ and DTIC.
* Prior therapy with biologic agents (including IL-2, interferon, bevacizumab, vaccines and immunostimulants) and signal transduction inhibitors (including sorafenib, erlotinib, sutent and elesclomol) are allowed.

Lower Dose Expanded Safety Cohorts Only

* Anti-coagulant restrictions for subjects that have tumor biopsies.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bhardwaj Desai, MD

Role: STUDY_DIRECTOR

Abbott

Countries

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United States

References

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Nuthalapati S, Munasinghe W, Giranda V, Xiong H. Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with Temozolomide in Subjects with Nonhematologic Malignancies. Clin Pharmacokinet. 2018 Jan;57(1):51-58. doi: 10.1007/s40262-017-0547-z.

Reference Type RESULT
PMID: 28497258 (View on PubMed)

Other Identifiers

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M06-862

Identifier Type: -

Identifier Source: org_study_id