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



Status:Recruiting
Conditions:Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:7/16/2013
Start Date:May 2010

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Phase I Study of ABT-888 in Combination With Gemcitabine in Patients With Advanced Malignancies


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


PRIMARY OBJECTIVES:

I. Establish the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the
combination of ABT-888 and gemcitabine (gemcitabine hydrochloride) in patients with advanced
solid tumors.

SECONDARY OBJECTIVES:

I. Establish the safety and tolerability of the combination of ABT-888 and gemcitabine in
patients with solid tumors.

II. Determine the effects of ABT-888 and gemcitabine treatment on DNA damage response by
analysis of markers such as Ataxia telangiectasia mutated (ATM) in peripheral blood
mononuclear cells (PBMCs).

III. Determine the pharmacokinetics of ABT-888 and gemcitabine when administered in
combination.

IV. Determine the generation of gemcitabine triphosphate in PBMCs. V. Document any evidence
of antitumor response.

OUTLINE: This is a dose-escalation study.

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.

After completion of study therapy, patients are followed up for at least 4 weeks.

NOTE: *Patients previously enrolled on a 4-week schedule (ABT-888 twice daily on days 1-21
with gemcitabine IV over 30 minutes once weekly on days 1, 8, and 15, and courses repeating
every 28 days) will continue on the 4-week schedule.

Inclusion Criteria:

- 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

- Bilirubin < 2.0 mg/dL

- AST and ALT < 3 times upper limit of normal

- Creatinine normal OR creatinine clearance > 50 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to swallow pills

- HIV-positive patients allowed provided that CD4 counts are < 500 and not on protease
inhibitors

- No uncontrolled diarrhea

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would limit compliance with study
requirements

- No other concurrent anticancer therapies or agents

- More than 4 weeks since prior major surgery, radiotherapy, or chemotherapy (6 weeks
for mitomycin C or nitrosoureas) and recovered

- Prior gemcitabine hydrochloride or PARP inhibition therapy, including ABT-888,
allowed

- No prior combination of gemcitabine hydrochloride and any PARP inhibitor

- Concurrent bisphosphonate IV allowed provided treatment was initiated before study
therapy (for patients with bone metastases or hypercalcemia)

- Patients with prostate cancer must continue luteinizing-hormone releasing-hormone
agonist therapy and discontinue antiandrogens (≥ 6 weeks since bicalutamide and ≥ 4
weeks since flutamide)

- No other concurrent investigational agents
We found this trial at
4
sites
4200 Fifth Ave
Pittsburgh, Pennsylvania 15260
(412) 624-4141
University of Pittsburgh The University of Pittsburgh is a state-related research university, founded as the...
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500 University Dr
Hershey, Pennsylvania 17033
(717) 531-6955
Penn State Milton S. Hershey Medical Center Penn State Milton S. Hershey Medical Center, Penn...
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Pittsburgh, Pennsylvania 15232
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