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NeoplasmsPhase 1NCT01419548

ABT-888, Carboplatin, and Paclitaxel for Cancer With Liver or Kidney Problems

A Phase 1 study testing ABT-888, Carboplatin and Paclitaxel in people with Neoplasms, run by National Cancer Institute (NCI) at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Background: Paclitaxel and carboplatin are two standard drugs that stop cancer cells from reproducing. ABT-888 is an experimental cancer drug that may prevent cancer cells from "fixing" the damage done by chemotherapy drugs. This may make the chemotherapy work better. Read more about this study

Who is it for?
Ages 18 to 110 years
Conditions the study is for
Neoplasms
What is being tested?
ABT-888, Carboplatin and Paclitaxel
How many people
0 participants
Where
2 sitesUnited States
Study dates
29 Jul 2011to 18 Nov 2011
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 to 110 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable, for which standard curative or palliative measures do not exist or are no longer effective, and for which there is expectation of response to the combination of carboplatin/paclitaxel (e.g., lung, ovarian, breast, melanoma).
  • Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of ABT-888 in patients < 18 years of age, children are excluded from this study, but may be eligible for future pediatric phase 1 combination trials.
  • ECOG performance status less than or equal to 2.
  • Life expectancy of greater than 12 weeks.
  • Patients must have marrow function as defined below:
  • absolute neutrophil count greater than or equal to 1,500/mcL
Show all 14Show fewer
  • platelets greater than or eqaul to 100,000/mcL
  • hemoglobin greater than or eqaul to 8.0 g/dL
  • Patients with all degrees of renal dysfunction are allowed including patients on hemodialysis. Patients with mild to severe hepatic dysfunction are allowed as defined below:
  • total bilirubin less than or eqaul to 5 times ULN AND AST and ALT less than or eqaul to10 times ULN
  • For patients with a recently placed biliary stent, patients should have consistent results within a hepatic group from two laboratory readings within 3 days apart, taken at least 10 days following biliary stent placement. For patients with a biliary stent placed over 2 months ago, no obstruction or blockage can have occurred within the last 2 months.
  • -The effects of ABT-888 on the developing human fetus are unknown. For this reason and because other therapeutic agents or modalities used in this trial are known to be teratogenic, 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • -Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those whose adverse event due to agents administered more than 4 weeks earlier have not resolved or stabilized. Patients who have been administered ABT-888 as part of a single or combination, Phase 0 or I study, should not necessarily be excluded from participating in this study solely because of receiving prior ABT-888.
  • Patients may not be receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or other agents used in study.
  • Peripheral neuropathy of severity greater than grade 1.
  • Inability to take oral medications on a continuous basis.
  • Evidence of bleeding diathesis.
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  • Patients with brain metastasis should have stable disease for at least 4 weeks following therapy for brain metastasis (such as surgery, radiotherapy or stereotactic radiosurgery).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because ABT-888 is PARP inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ABT-888, breastfeeding should be discontinued if the mother is treated with ABT-888. These potential risks may also apply to other agents used in this study.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with ABT-888 as well as possible interactions with paclitaxel. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. However, HIV-positive patients without an AIDS-defining diagnosis who are not receiving agents with the potential for PK interactions with ABT-888 may be eligible.
  • Patients with both hepatic and renal dysfunction will also be excluded.
  • Patients who received and progressed on the combination of carboplatin/paclitaxel will not be eligible.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

  • University of Pittsburgh Cancer Center

    Pittsburgh, Pennsylvania

Other trials in United States

About this study

Official title: An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors

Background:

  • Paclitaxel and carboplatin are two standard drugs that stop cancer cells from reproducing. ABT-888 is an experimental cancer drug that may prevent cancer cells from "fixing" the damage done by chemotherapy drugs. This may make the chemotherapy work better. More tests are needed to determine the safety and effectiveness of ABT-888 plus chemotherapy. Researchers also want to find the best dose of ABT-888 for people who have kidney or liver problems in addition to cancer.
Read more

Objectives:

  • To test the safety and effectiveness of ABT-888 plus carboplatin and paclitaxel in people who have both cancer and kidney or liver problems.

Eligibility:

  • Individuals at least 18 years of age who have solid tumors that have not responded to standard treatment, and who also have kidney or liver problems.
  • A small group of people with solid tumors and normal kidney and liver function may also receive treatment for study comparison purposes.

Design:

  • Participants will be screened with a medical history and physical exam. They will have blood and urine tests, tumor samples, tests of liver and kidney function, and imaging studies. Participants will also provide a hair sample at the start of the study.
  • Participants will take one dose of ABT-888 1 week before starting chemotherapy. The two chemotherapy drugs will be given on day 3 of a 21-day cycle. Participants will take ABT-888 daily for the first 7 days of each cycle.
  • They will keep a diary to record medication doses and any side effects. They will also have frequent blood tests and imaging studies. Participants will provide more hair samples on day 3 of cycle 1 before and after having paclitaxel.
  • Participants will continue treatment for up to 18 weeks as long as the cancer stops growing or shrinks and there are no serious side effects. Participants may have the option to continue treatment after the study is done.
Read the detailed description

Background:

The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining genomic stability by regulating a variety of DNA repair mechanisms. The carboplatin/paclitaxel combination has demonstrated a wide spectrum of clinical antitumor activity, making it an ideal platform for evaluation with novel agents, such as the PARP inhibitor ABT-888.

Objectives:

To determine the pharmacokinetics and pharmacodynamics of ABT-888 in patients with varying degrees of renal or hepatic dysfunction.

To determine the maximum tolerated dose (MTD) of ABT-888 in combination with carboplatin and paclitaxel for patients with varying degrees of liver or kidney dysfunction.

To provide dosing recommendations for ABT-888 in combination with carboplatin and paclitaxel based on degree of hepatic and renal impairment.

To define the dose-limiting toxicity and other toxicities associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction.

To evaluate the pharmacokinetic parameters of ABT-888, carboplatin and paclitaxel when administered as a combination in patients with varying degrees of renal or hepatic dysfunction.

To evaluate the pharmacodynamic measurement of PAR and platinum adducts in peripheral blood mononuclear cells (PBMC) and tumor cells associated with the use of this combination

in patients with varying degrees of renal or hepatic dysfunction.

Eligibility:

Patients must have histologically confirmed malignancy that is metastatic or unresectable, for which standard curative or palliative measures do not exist or are no longer effective, and for which there is expectation of response to the combination of carboplatin/paclitaxel (e.g., lung, ovarian, breast, and melanoma).

Patients must have adequate bone marrow function.

Patients with normal organ function, patients with all degrees of renal dysfunction, and patients with mild to severe hepatic dysfunction are allowed.

Study Design:

ABT-888 (80 mg) will be given orally on day -6 ( 1 day) of cycle 1 in all cohorts. ABT-888 in varying doses will then be given on days 1-7 of each cycle, with the dose depending on each patient's degree of renal or hepatic dysfunction.

Fixed doses of chemotherapy will be given intravenously on day 3 of each cycle. For patients with renal dysfunction, carboplatin will be given at AUC of 6 and paclitaxel at 175 mg/m2. For patients with hepatic dysfunction, carboplatin will be given at AUC of 6 and paclitaxel at doses adjusted to each patient's degree of hepatic dysfunction.

The dose of ABT-888 will be escalated to determine the MTD of the combination.

Conditions
Neoplasms
Being tested
ABT-888, Carboplatin, Paclitaxel
Keywords
ABT-888, Liver Dysfunction, Kidney Dysfunction, PARP Inhibitor, Pharmacokinetics, Cancer
Medical subject headings
Neoplasms, Liver Diseases

What participants receive

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

What is being measured

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

  1. To determine the pharmacokinetics and pharmacodynamics of ABT-888 in patients with varying degrees of renal or hepatic dysfunction. To determine the MTD of ABT-888 with carboplatin and paclitaxel in these patients.

  2. To determine the pharmacokinetics and pharmacodynamics of ABT-888 in patients with varying degrees of renal or hepatic dysfunction.

  3. To determine the MTD of ABT-888 with carboplatin and paclitaxel in these patients.

Secondary outcomes (1)

  1. To define the dose-limiting toxicity and other toxicities associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction.

Timeline

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

  1. First posted18 Aug 2011 (estimated)
  2. Study start29 Jul 2011
  3. Primary completion18 Nov 2011
  4. Study completion18 Nov 2011

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01419548
Sponsor's protocol ID
110215
Other IDs
11-C-0215
Status last verified
18 Nov 2011
First submitted
17 Aug 2011
Last updated
2 Jul 2017
Results posted
No

Publications

  • Ame JC, Spenlehauer C, de Murcia G. The PARP superfamily. Bioessays. 2004 Aug;26(8):882-93. doi: 10.1002/bies.20085.

    PubMed 15273990

  • Shiobara M, Miyazaki M, Ito H, Togawa A, Nakajima N, Nomura F, Morinaga N, Noda M. Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 2001 Mar;16(3):338-44. doi: 10.1046/j.1440-1746.2001.02378.x.

    PubMed 11339428

  • Tomoda T, Kurashige T, Moriki T, Yamamoto H, Fujimoto S, Taniguchi T. Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma. Am J Hematol. 1991 Aug;37(4):223-7. doi: 10.1002/ajh.2830370402.

    PubMed 1907096

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ABT-888, Carboplatin and Paclitaxel in people with Neoplasms, run by National Cancer Institute (NCI) at 2 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 14 inclusion and 12 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: withdrawn, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 withdrawn before enrolling participants, so there are no results.

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?

To determine the pharmacokinetics and pharmacodynamics of ABT-888 in patients with varying degrees of renal or hepatic dysfunction. To determine the MTD of ABT-888 with carboplatin and paclitaxel in these patients.. The study lists 3 primary outcomes in all. 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 NCT01419548, which also lists 3 linked publications.

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 2017.

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