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Advanced Adult Primary Liver CancerPhase 1NCT01282333

Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

A Phase 1 study testing gemcitabine hydrochloride, veliparib and diagnostic laboratory biomarker analysis in people with Advanced Adult Primary Liver Cancer and Localized Unresectable Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I clinical trial is studying the side effects and best dose of veliparib and gemcitabine hydrochloride when given with cisplatin in treating patients with advanced biliary, pancreatic, urothelial, or non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
gemcitabine hydrochloride, veliparib and diagnostic laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
3 sitesUnited States
Study dates
Jan 2011to Feb 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

  • Patients must have histologically or cytologically confirmed advanced biliary/pancreatic cancer, urothelial cancer, or non-small cell lung cancer that is metastatic or unresectable
  • Patients with known CNS metastases should be excluded from this clinical trial
  • ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  • Life expectancy of greater than 12 weeks
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
Show all 31Show fewer
  • Total bilirubin within normal institutional limits
  • AST/ALT ≤ 2.5 times institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min
  • QTc interval on ECG ≤ 0.48 seconds by Bazett's calculation (≤ CTCAE v.4 grade 2)
  • Not pregnant or nursing
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • Patients must be able to swallow pills and have no significant impairment in gastrointestinal absorption
  • Patients with known or suspected germline mutation in BRCA1 or BRCA2 are eligible to participate
  • Patients in study screening (primarily those with pancreatic cancer) who have a family history that is suspicious for BRCA1 or BRCA2 germline mutation should be assessed by the BRCAPRO computer program to quantitate the likelihood of harboring a deleterious BRCA mutation
  • Patients found to have a BRCAPRO probability score of ≥ 20% should undergo formal full-sequence BRCA testing
  • Patients in screening with a BRCAPRO probability of ≥ 20% who decline genetic testing are not eligible to participate in this trial due to the potential to confound safety assessment
  • No uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • HIV-positive patients are eligible
  • No active seizure or history of seizure disorder
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib (ABT-888) or other agents used in this study
  • No peripheral neuropathy greater than grade1
  • No prior systemic treatment
  • No prior cytotoxic chemotherapy (neoadjuvant, adjuvant, or metastatic setting)
  • At least 4 weeks since major surgery or radiation therapy
  • Patients may not be receiving any other investigational agents

Who cannot join

None listed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: Phase I Study of Veliparib (ABT-888) in Combination With Cisplatin Plus Gemcitabine in Advanced Biliary, Pancreatic, Urothelial, and Non-small Cell Lung Cancer

This phase I clinical trial is studying the side effects and best dose of veliparib and gemcitabine hydrochloride when given with cisplatin in treating patients with advanced biliary, pancreatic, urothelial, or non-small cell lung cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and 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 more than one drug (combination chemotherapy) may kill more tumor cells. Veliparib may help cisplatin and gemcitabine hydrochloride work better by making tumor cells more sensitive to the drugs.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum-tolerated dose of veliparib (ABT-888) (days 1-12 of a 21-day schedule) in combination with cisplatin (day 3) and gemcitabine (days 3, 10) in patients with advanced, previously untreated carcinoma of the bile ducts, gallbladder or pancreas, non-small cell lung cancer, or transitional cell carcinoma of the bladder/urothelial tract.

SECONDARY OBJECTIVES:

  1. Describe the dose-limiting toxicity (DLT) and other toxicities associated with veliparib in combination with cisplatin plus gemcitabine as assessed by CTCAE v4.0.

II. Determine the recommended phase 2 dose of veliparib (ABT-888) (RP2D) in combination with cisplatin plus gemcitabine.

III. Document anti-tumor activity of veliparib (ABT-888), cisplatin, and gemcitabine as assessed by RECIST 1.1.

IV. Determine the plasma pharmacokinetics of veliparib (ABT-888), cisplatin, and gemcitabine.

  1. Determine the abundance of gemcitabine triphosphate in PBMCs following gemcitabine administration.

VI. Measure the abundance of DNA-platinum adducts in tumor tissue following cisplatin administration.

VII. Measure PARP enzymatic activity in PBMC and tumor tissue following study treatment.

VIII. Perform an exploratory correlation between abundance of BRCA and other proteins assessed by tumor immunohistochemistry and clinical response.

OUTLINE: This is a multicenter, dose-escalation study of veliparib and gemcitabine hydrochloride. Patients are stratified according to presence of suspected or known BRCA mutations (no vs yes).

Patients receive veliparib orally every 12 hours on days 1-12, gemcitabine hydrochloride IV over 30 minutes on days 3 and 10, and cisplatin IV over 60-120 minutes on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with suspected or known germline BRCA mutations may continue to receive single-agent veliparib continuously in the absence of disease progression or unacceptable toxicity. Patients may undergo blood, tumor tissue, and hair follicle sample collection periodically for pharmacokinetic and correlative studies.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
gemcitabine hydrochloride, veliparib, diagnostic laboratory biomarker analysis, pharmacological study, cisplatin
Medical subject headings
Urinary Bladder Neoplasms, Pancreatic Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • gemcitabine hydrochlorideDrug

    Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

    Given IV

  • veliparibDrug

    Also called ABT-888

    Given orally

  • diagnostic laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • cisplatinDrug

    Also called CACP, CDDP, CPDD, DDP

    Given IV

Study groups in NCT01282333
Study groupRoleWhat they receive
Treatment (veliparib, gemcitabine hydrochloride, cisplatin)ExperimentalPatients receive veliparib orally every 12 hours on days 1-12, gemcitabine hydrochloride IV over 30 minutes on days 3 and 10, and cisplatin IV over 60-120 minutes on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with suspected or known germline BRCA mutations may continue to receive single-agent veliparib continuously in the absence of disease progression or unacceptable toxicity. Patients may undergo blood, tumor tissue, and hair follicle sample collection periodically for pharmacokinetic and correlative studies.
Receives: Drug: gemcitabine hydrochloride; Drug: veliparib; Other: diagnostic laboratory biomarker analysis; Other: pharmacological study; Drug: cisplatin

What is being measured

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

  1. Maximum-tolerated dose of veliparib in combination with cisplatin and gemcitabine

    The maximum toxicity for each category of interest that are determined to be possibly, probably or definitely related to study treatment will be recorded for each patient and the summary results will be tabulated (according to CTCAE v4.0).

    Measured: 21 days

Secondary outcomes (2)

  1. Dose-limiting and other toxicities according to CTCAE v4.0

    Measured: Up to 4 weeks post-treatment

  2. Recommended phase II dose

    Measured: Up to 4 weeks post-treatment

Timeline

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

  1. First posted25 Jan 2011 (estimated)
  2. Study startJan 2011
  3. Primary completionFeb 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
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01282333
Sponsor's protocol ID
NCI-2011-02576
Other IDs
UPCI 10-037, CDR0000693751, PCI-10-037, U01CA099168
Status last verified
Jul 2013
First submitted
22 Jan 2011
Last updated
2 Jul 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing gemcitabine hydrochloride, veliparib and diagnostic laboratory biomarker analysis in people with Advanced Adult Primary Liver Cancer and Localized Unresectable Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 3 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 31 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: stopped early, as of the sponsor's last update on 2 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 was stopped early. Results are not available in the source record.

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?

Maximum-tolerated dose of veliparib in combination with cisplatin and gemcitabine (time frame: 21 days). 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 NCT01282333.

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 2013.

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