ABT-888 and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors

NCT01154426 | Completed Phase 1

• 6 other identifiers: NCI-2011-01473CDR000067361309-0128324P30CA047904U01CA099168
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 4

Brief Summary

This phase I trial is studying the side effects and best dose of giving ABT-888 together with gemcitabine hydrochloride in treating patients with advanced solid tumors. ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with gemcitabine hydrochloride may kill more tumor cells.

Conditions

Adult Solid Neoplasm; BRCA1 Mutation Carrier; BRCA2 Mutation Carrier

Outcome Measures

Primary Outcomes (1)

• MTD of ABT-888 and gemcitabine hydrochloride, determined according to incidence of DLT graded using the NCI CTCAE version 4.0

  3 weeks

Secondary Outcomes (3)

• Adverse events as assessed by NCI CTCAE v 4.0

  Up to 4 weeks after completion of study treatment

• Plasma concentrations of gemcitabine hydrochloride and ABT-888

  Pre-drug, 25, 60, and 90 min, 2, 3, 4, 6, and 8 hours post-ABT-888 on day -2; pre-drug, 15, 25 (before end of gemcitabine infusion), 60, and 90 min, 2, 3, 4, 6, 8, 24, and 48 h after the start of gemcitabine hydrochloride infusion on day 1 of course 1

• Response (complete or partial response)

  Up to 4 weeks after completion of study treatment

Study Arms (1)

Treatment (gemcitabine hydrochloride and ABT-888)

EXPERIMENTAL

Patients receive oral ABT-888 twice daily on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21\* days in the absence of disease progression or unacceptable toxicity.

Other: Diagnostic Laboratory Biomarker Analysis; Drug: Gemcitabine Hydrochloride; Other: Pharmacological Study; Drug: Veliparib

Interventions

Diagnostic Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (gemcitabine hydrochloride and ABT-888)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011

Treatment (gemcitabine hydrochloride and ABT-888)

Pharmacological Study OTHER

Correlative studies

Treatment (gemcitabine hydrochloride and ABT-888)

Veliparib DRUG

Given orally

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Treatment (gemcitabine hydrochloride and ABT-888)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed solid tumors meeting 1 of the following criteria:
• Progressive disease following standard therapy
• Disease for which acceptable standard treatment options do not exist
• May have received 0-2 prior chemotherapeutic regimens (single-agent or combination chemotherapies)
• Willing to undergo BRCA mutation analysis
• Known BRCA mutations allowed
• All patients, at any dose level, without a known BRCA mutation undergo screening with the BRCAPRO program to assess the likelihood of having a BRCA mutation
• Patients with a BRCAPRO likelihood of gene mutation of ≥ 20% must undergo BRCA gene testing by the Myriad Genetic Laboratories in order to participate in the study
• Patients are eligible whether they have a known deleterious BRCA 1 or 2 mutation or a mutation of uncertain significance
• No CNS disease (e.g., brain metastases or glioma)
• No active seizure or history of seizure disorder
• ECOG performance status 0-2 (Karnofsky 60-100%)
• Life expectancy \> 3 months
• ANC ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

UPMC-Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Manzo J, Puhalla S, Pahuja S, Ding F, Lin Y, Appleman L, Tawbi H, Stoller R, Lee JJ, Diergaarde B, Kiesel BF, Yu J, Tan AR, Belani CP, Chew H, Garcia AA, Morgan RJ, Wahner Hendrickson AE, Visscher DW, Hurley RM, Kaufmann SH, Swisher EM, Oesterreich S, Katz T, Ji J, Zhang Y, Parchment RE, Chen A, Duan W, Giranda V, Shepherd SP, Ivy SP, Chu E, Beumer JH; ETCTN-8282 study team. A phase 1 and pharmacodynamic study of chronically-dosed, single-agent veliparib (ABT-888) in patients with BRCA1- or BRCA2-mutated cancer or platinum-refractory ovarian or triple-negative breast cancer. Cancer Chemother Pharmacol. 2022 May;89(5):721-735. doi: 10.1007/s00280-022-04430-6. Epub 2022 Apr 18.

  PMID: 35435472 DERIVED

MeSH Terms

Interventions

Gemcitabine; veliparib

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Ronald Stoller

  University of Pittsburgh Cancer Institute (UPCI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: June 30, 2010
• Study Start: May 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: July 2, 2015

Record last verified: 2014-12

Locations

US (4)