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Adult Solid NeoplasmPhase 1NCT01154426

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

A Phase 1 study testing Diagnostic Laboratory Biomarker Analysis, Gemcitabine Hydrochloride and Pharmacological Study in people with Adult Solid Neoplasm and BRCA1 Mutation Carrier, run by National Cancer Institute (NCI) at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Diagnostic Laboratory Biomarker Analysis, Gemcitabine Hydrochloride and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
4 sitesUnited States
Study dates
May 2010to Oct 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 37Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • UPMC-Magee Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Diagnostic Laboratory Biomarker Analysis, Gemcitabine Hydrochloride, Pharmacological Study, Veliparib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Diagnostic Laboratory Biomarker AnalysisOther

    Correlative studies

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011

    Given IV

  • Pharmacological StudyOther

    Correlative studies

  • VeliparibDrug

    Also called ABT-888, PARP-1 inhibitor ABT-888

    Given orally

Study groups in NCT01154426
Study groupRoleWhat they receive
Treatment (gemcitabine hydrochloride and ABT-888)ExperimentalPatients 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.
Receives: Other: Diagnostic Laboratory Biomarker Analysis; Drug: Gemcitabine Hydrochloride; Other: Pharmacological Study; Drug: Veliparib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 3 weeks

Secondary outcomes (3)

  1. Adverse events as assessed by NCI CTCAE v 4.0

    The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. We will describe all DLTs and other serious (≥ grade 3) on a patient-by-patient basis; descriptions will include dose level and any relevant baseline data. Statistics on the number of cycles received by patients and any dose reductions will be tabulated.

    Measured: Up to 4 weeks after completion of study treatment

  2. Plasma concentrations of gemcitabine hydrochloride and ABT-888

    Plasma concentration versus time data will be analyzed non-compartmentally using PK Solutions 2.0. Data may also be analyzed using compartmental methods as implemented by the ADAPT computer program or a suitable commercially available software package. Relationships between pharmacokinetic and pharmacodynamic data will be explored and evaluated using the ADAPT computer program or a suitable commercially available software packages.

    Measured: 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

  3. Response (complete or partial response)

    Responses and incidence of stable disease will be tabulated by disease diagnosis and by dose level; no formal statistical analyses are planned.

    Measured: Up to 4 weeks after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionOct 2013
  4. Study completionOct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01154426
Sponsor's protocol ID
NCI-2011-01473
Other IDs
NCI-2011-01473, CDR0000673613, 09-012, 8324, P30CA047904, U01CA099168
Status last verified
Dec 2014
First submitted
29 Jun 2010
Last updated
2 Jul 2015
Results posted
No

Publications

  • 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.

    PubMed 35435472

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Diagnostic Laboratory Biomarker Analysis, Gemcitabine Hydrochloride and Pharmacological Study in people with Adult Solid Neoplasm and BRCA1 Mutation Carrier, run by National Cancer Institute (NCI) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of ABT-888 and gemcitabine hydrochloride, determined according to incidence of DLT graded using the NCI CTCAE version 4.0 (time frame: 3 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01154426, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2015; AzTrials last refreshed its copy on 7 Nov 2026.

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