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Metastatic Malignant Solid NeoplasmPhase 1/2NCT01012817

Veliparib and Topotecan Hydrochloride in Treating Patients With Solid Tumors, Relapsed or Refractory Ovarian Cancer, or Primary Peritoneal Cancer

A Phase 1/2 study testing Laboratory Biomarker Analysis, Pharmacogenomic Study and Pharmacological Study in people with Metastatic Malignant Solid Neoplasm and Recurrent Fallopian Tube Carcinoma, run by National Cancer Institute (NCI) at 15 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase I/II trial studies the side effects and best dose of veliparib and topotecan hydrochloride and to see how well they work in treating patients with solid tumors, ovarian cancer that has come back or does not respond to treatment, or primary peritoneal cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacogenomic Study and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
15 sitesUnited States
Study dates
3 Nov 2009to 10 Mar 2027
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • PHASE I: Adult patients with histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative measures or other therapy definitely capable of extending life expectancy does not exist
  • PHASE II: All patients enrolled in the Phase II portion of this trial must have a history of biopsy-proven ovarian, fallopian tube or primary peritoneal cancer
  • Patients must have received < 3 lines of prior therapy and have relapsed less than a year from their last platinum regimen; regimens that are used twice (for example carboplatin and paclitaxel) can be counted as one; if a regimen is changed during the course of treatment due to side effect profile or allergy, the course of therapy is counted as one regimen; (for example, if docetaxel is substituted for paclitaxel due to a reaction during the initial course of adjuvant therapy, this is considered one regimen)
  • Patients must have measurable disease with at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm with conventional techniques or as >= 1.0 cm with spiral computed topography (CT); if spiral CT is used, it must be used for both pre- and post- treatment tumor assessments
  • Absolute neutrophil count >= 1500/mcL
  • Hemoglobin >= 9.0 g/dL
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  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x the upper limit of normal (ULN)
  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) or serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 x ULN in the absence of hepatic metastasis; SGPT (ALT) =< 3 x ULN or SGOT (AST) =< 5 x ULN in the presences of hepatic metastasis
  • Creatinine =< 1.5 x ULN
  • International normalized ratio (INR) =< 1.4 unless receiving therapeutic doses of coumadin
  • Partial thromboplastin time (PTT) =< 48 seconds (1.25 x ULN)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Ability to provide informed consent
  • Willingness to return to enrolling institution for follow up
  • Life expectancy >= 12 weeks
  • Willingness to provide the biologic specimens is required by the protocol; this is part of the mandatory correlative research component; these specimens include:
  • PHASE I: peripheral blood for plasma pharmacokinetic analysis and peripheral blood mononuclear cell (PBMC) polymer assessment from 0-24 h after drug administration on days 1 and 2 of cycle 1 as well as day 2 of cycle 2; urine for assessment of ABT-888 renal clearance for 24 h after administration of drugs on days 1 and 2 of cycle 1 as well as day 2 of cycle 2; and a pretreatment peripheral blood sample for possible sequencing of the BRCA1, BRCA2 loci as well as possible pharmacogenomic analysis
  • Negative urine or serum pregnancy test done =< 7 days prior to registration for females of child bearing potential only
  • Able to swallow and absorb the medication

Who cannot join

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Prior treatment with a PARP inhibitor or topotecan
  • 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
  • Any of the following prior therapies:
  • Chemotherapy =< 4 weeks prior to registration
  • Mitomycin C/nitrosoureas =< 6 weeks prior to registration
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  • Immunotherapy =< 4 weeks prior to registration
  • Biologic therapy =< 4 weeks prior to registration
  • Radiation therapy =< 4 weeks prior to registration
  • Radiation to > 25% of bone marrow
  • Investigational therapy or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) =< 4 weeks prior to registration; subjects with prostate cancer will be permitted to continue hormone therapy
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • New York Heart Association classification III or IV
  • Known central nervous system (CNS) metastases or seizure disorder; patients with known brain metastases that have been successfully treated and stable for >= 6 months without requirement for corticosteroids and without seizure activity will be eligible
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy, except non-melanotic skin cancer or carcinoma-in-situ of the cervix
  • Note: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
  • History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • More than 2 prior chemotherapy regimens for the current malignancy; full dose chemotherapy used in conjunction with concurrent radiation therapy will be included as prior therapy
  • Note: Prior hormonal therapy (e.g. leuprolide, aromatase inhibitors, tamoxifen) and immunotherapy will be allowed and not included as a prior chemotherapy; if the chemotherapy regimen is altered during the course due to issues with tolerability or safety, the regimen will be counted as one; using the same regimen at recurrence is counted as one regimen; the addition of bevacizumab to a prior regimen is considered one regimen

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • University of Chicago Medicine-Orland Park

    Orland Park, Illinois, 60462

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A Phase 1/2 Trial of ABT-888, an Inhibitor of Poly(ADP-ribose) Polymerase (PARP), and Topotecan (TPT) in Patients With Solid Tumors (Phase 1) and Relapsed Ovarian Cancer or Primary Peritoneal Cancer (Phase 2) After Prior Platinum Containing First-Line Chemotherapy

This phase I/II trial studies the side effects and best dose of veliparib and topotecan hydrochloride and to see how well they work in treating patients with solid tumors, ovarian cancer that has come back or does not respond to treatment, or primary peritoneal 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 topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib with chemotherapy may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose of the combination of veliparib (ABT-888) and weekly topotecan (topotecan hydrochloride) in adult patients with advanced solid tumors. (Phase I) II. To identify any anti-tumor activity of this treatment combination, as assessed by objective response in patients with advanced solid tumors. (Phase I) III. To assess the confirmed response rate for patients with epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma treated with the combination of ABT-888 and weekly topotecan.

IV. To assess the progression free response (PFS) for patients with epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma treated with the combination of ABT-888 and weekly topotecan. (Phase II)

SECONDARY OBJECTIVES:

  1. To identify any pharmacokinetic interactions between ABT-888 and topotecan. (Phase I) II. To determine whether topotecan stimulates adenosine diphosphate (ADP)-ribose polymer formation in circulating peripheral blood mononuclear cells. (Phase I) III. To determine whether ABT-888 inhibits basal or topotecan-stimulated ADP-ribose polymer formation. (Phase I) IV. To assess differences in the toxicity and/or efficacy of this regimen based on BRCA 1/2 mutational status. (Phase II) V. To determine whether pretreatment tumor cell levels of topoisomerase I, poly ADP-ribose polymerase (PARP), BRCA1, BRCA2, XRCC1, tyrosyl-deoxyribonucleic acid (DNA) phosphodiesterase 1 (TDP1), P-glycoprotein or breast cancer resistance protein (BCRP) predict response to this regimen. (Phase II) VI. To identify, in an exploratory manner, any transcriptional profiles that may predict response to this regimen. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of veliparib and topotecan hydrochloride followed by a phase II study. (PHASE I DOSE-ESCALATION PART IS COMPLETED)

Patients receive veliparib orally (PO) on days 1-3, 8-10, and 15-17 (veliparib is omitted on days 1-3 of course 2) and topotecan hydrochloride intravenously (IV) over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3 months (Phase I) or every 3 or 6 months for 5 years (Phase II).

Being tested
Laboratory Biomarker Analysis, Pharmacogenomic Study, Pharmacological Study, Topotecan Hydrochloride, Veliparib
Medical subject headings
Neoplasm Metastasis, Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacogenomic StudyOther

    Also called PHARMACOGENOMIC

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Topotecan HydrochlorideDrug

    Also called Evotopin, Hycamptamine, Hycamtin, Nogitecan Hydrochloride

    Given IV

  • VeliparibDrug

    Also called ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

    Given PO

Study groups in NCT01012817
Study groupRoleWhat they receive
Treatment (veliparib and topotecan hydrochloride)ExperimentalPatients receive veliparib PO on days 1-3, 8-10, and 15-17 (veliparib is omitted on days 1-3 of course 2) and topotecan hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study; Other: Pharmacological Study; Drug: Topotecan Hydrochloride; Drug: Veliparib

What is being measured

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

  1. Maximum Tolerated Dose of Topotecan Hydrochloride and Veliparib, Determined According to Incidence of Dose-limiting Toxicity, Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)

    The number of patients with a dose limiting toxicity will be reported. Dose-limiting toxicity (DLT) will be defined as a cycle 1 adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria: Grade 4 anemia, grade 4 neutrophil count decrease, grade 4 platelet count decrease, Serum creatinine >= 2 times baseline or ≥ 2 times the upper limit of normal if baseline is < the upper limit of normal, or other >= Grade 3 as per NCI Common Terminology Criteria for Adverse Events CTCAE version 4.0. >= Grade 3 nausea, vomiting, or diarrhea with maximal supportive treatment(s) will be considered dose-limiting. Grade 3 fatigue or anorexia will not be considered dos

    Measured: 4 weeks

  2. Percent of Patients With Tumor Response, Defined as Complete Response or Partial Response as Assessed Using Response Evaluation Criteria In Solid Tumors

    The proportion of successes will be estimated by the number of successes(CR or PR) divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner (1987). Complete Response (CR) is defined as disappearance of all target lesions and, if non target lesions exist, the disappearance of all non-target lesions and normalization of tumor maker level. At least 30% decrease in the sum of the longest diameter (LD) of target lesion taking as reference the baseline sum.

    Measured: Up to 48 weeks (12 courses)

Secondary outcomes (5)

  1. Overall Survival

    The distribution of survival time for phase 2 patients will be estimated using the method of Kaplan-Meier.

    Measured: The time from registration to death due to any cause, assessed up to 5 years

  2. Progression Free Survival

    The distribution of progression free survival will be estimated using the method of Kaplan-Meier.

    Measured: The time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years

  3. Duration of Response

    Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a complete response or partial response to the earliest date progression is documented.

    Measured: Up to 5 years

  4. Time to Treatment Failure

    Time to treatment failure is defined to be the time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal.

    Measured: The time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal, assessed up to 5 years

  5. Adverse Events, Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

    Measured: Up to 5 years

Timeline

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

  1. First posted13 Nov 2009 (estimated)
  2. Study start3 Nov 2009
  3. Primary completion13 Jan 2019
  4. Study completion10 Mar 2027 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
88 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01012817
Sponsor's protocol ID
NCI-2011-00312
Other IDs
NCI-2011-00312, 09-000742, MC0861, MAYO-MC0861, CDR0000657976, 8329, 8329, P50CA136393
Status last verified
Sep 2026
First submitted
11 Nov 2009
Last updated
14 Sep 2026
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Laboratory Biomarker Analysis, Pharmacogenomic Study and Pharmacological Study in people with Metastatic Malignant Solid Neoplasm and Recurrent Fallopian Tube Carcinoma, run by National Cancer Institute (NCI) at 15 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 20 inclusion and 26 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: under way, not looking for participants, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Topotecan Hydrochloride and Veliparib, Determined According to Incidence of Dose-limiting Toxicity, Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I) (time frame: 4 weeks). The study lists 2 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 NCT01012817.

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 14 Sep 2026.

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