Adult Solid NeoplasmPhase 1NCT00535119
Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
A Phase 1 study testing Carboplatin, Laboratory Biomarker Analysis and Paclitaxel in people with Adult Solid Neoplasm and BRCA1 Mutation Carrier, run by National Cancer Institute (NCI) at 7 sites in United States.
Trial summary
This phase I trial is studying the side effects and best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with advanced solid cancer. Veliparib 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
- Conditions the study is for
- Adult Solid Neoplasm, BRCA1 Mutation Carrier, BRCA2 Mutation Carrier
- What is being tested?
- Carboplatin, Laboratory Biomarker Analysis and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2007to Oct 2012
- 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 or cytologically confirmed advanced solid malignancy
- Patients enrolled in stratum II of the study must have BRCA1/2 mutation (added 04/07/09)
- Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment
- ECOG performance status 0-2
- Life expectancy > 12 weeks
- ANC ≥ 1,500/μL
Show all 16Show fewer
- Platelet count ≥ 100,000/μL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- More than 3 weeks since prior radiotherapy
- Prior veliparib allowed
Who cannot join
- Known history of allergic reactions to veliparib, carboplatin, or Cremophor-paclitaxel
- 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
Show all 15Show fewer
- Psychiatric illness or social situations that would preclude compliance with study requirements
- Peripheral neuropathy > grade 1
- Inability to take oral medications on a continuous basis
- Active seizure or history of seizure disorder
- Evidence of bleeding diathesis
- Received > 3 prior chemotherapy regimens for advanced stage disease for patients enrolled in stratum I (there is no upper limit on the number of prior regimens for patients enrolled in stratum II) (added 04/07/09)
- Adjuvant chemotherapy administered ≥ 2 years prior to enrollment to the study does not count as a prior chemotherapy regimen
- Other concurrent investigational agents
- Concurrent combination antiretroviral therapy for HIV-positive patients
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies
This phase I trial is studying the side effects and best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with advanced solid 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 carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with carboplatin and paclitaxel may help kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the recommended dose for phase II studies of veliparib (ABT-888 ) that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies. (Stratum I) II. To determine the recommended dose for phase II studies of veliparib that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies that harbor a germline BRCA1/2 mutation. (Stratum II) (added 04/07/09)
SECONDARY OBJECTIVES:
- To define the dose-limiting toxicity and other toxicities associated with the use of this combination.
II. To obtain preliminary evidence of antitumor activity in patients treated with this combination.
III. To evaluate the pharmacokinetic parameters of veliparib, carboplatin, and paclitaxel when administered as a combination.
IV. To conduct correlative science studies.
OUTLINE: This is a multicenter, dose-escalation study of veliparib. Patients are stratified according to BRCA status (no [stratum I] vs yes [stratum II]).
Patients receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib orally (PO) twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo peripheral blood mononuclear cell collection periodically for pharmacokinetic and biomarker studies.
After completion of study treatment, patients are followed up for 4 weeks.
- Conditions
- Adult Solid Neoplasm, BRCA1 Mutation Carrier, BRCA2 Mutation Carrier, Hereditary Breast and Ovarian Cancer Syndrome
- Being tested
- Carboplatin, Laboratory Biomarker Analysis, Paclitaxel, Pharmacological Study, Veliparib
- Medical subject headings
- Hereditary Breast and Ovarian Cancer Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
Correlative studies
VeliparibDrug
Also called ABT-888, PARP-1 inhibitor ABT-888
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy and chemotherapy) | Experimental | Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study; Drug: Veliparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose (RP2D) for each stratum
The RP2D for each cohort will be defined by the study separately. Standard up \& down dose-escalation scheme to determine the RP2D will be use, and toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Measured: Up to 4 weeks
Secondary outcomes (7)
Dose-limiting toxicity (DLT)
Toxicities should be attributable to the study drug(s) to constitute DLT. Patients will be considered evaluable for DLT if they are eligible, and if they receive any amount of treatment and experience DLT or complete the first course of treatment
Measured: During course 1
Frequency of platinum-DNA adducts
Changes will be summarized as means and standard deviations. A statistical test of the null hypothesis of no change in each variable will be done using the Wilcoxon signed-ranks procedure. Measurements of the two variables at additional time points will be analyzed in a descriptive fashion using tables and plots.
Measured: At baseline and 4 weeks post-treatment
Incidence of stable disease (SD)
SD is defined as neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started.
Measured: Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment
PAR levels
Changes will be summarized as means and standard deviations. A statistical test of the null hypothesis of no change in each variable will be done using the Wilcoxon signed-ranks procedure. Measurements of the two variables at additional time points will be analyzed in a descriptive fashion using tables and plots.
Measured: Up to 4 weeks post-treatment
Responses to veliparib in combination with carboplatin and paclitaxel
Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.
Measured: Up to 4 weeks post-treatment
Time to progression (TTP)
Progression will be evaluated in this study using the new international criteria proposed by RECIST. TTP will be displayed for all patients and for patients who have responded; no formal statistical analysis is planned.
Measured: Time from start of treatment to time of progression, assessed up to 4 weeks post-treatment
Toxicities as assessed by CTCAE v.4.0
Toxicities will be defined as regimen-related if they are possibly, probably or definitely related to treatment. 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, grade and dose level. Serious (≥ Grade 3) toxicities will be described on a patient-by-patient basis and will include any relevant baseline data.
Measured: From the time of their first treatment with veliparib to 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.
- First posted26 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Suresh Ramalingam, Principal investigator, University of Pittsburgh Cancer Institute (UPCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00535119
- Sponsor's protocol ID
- NCI-2009-00258
- Other IDs
- NCI-2009-00258, PCI-07-015, CDR0000566233, UPCI # 07-015, 7967, N01CM00038, P30CA047904, U01CA099168
- Status last verified
- Apr 2015
- First submitted
- 25 Sep 2007
- Last updated
- 22 May 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT00535119
- Acronym / sponsor ID
- NCI-2009-00258
- Conditions
- Adult Solid Neoplasm, BRCA1 Mutation Carrier, BRCA2 Mutation Carrier, Hereditary Breast and Ovarian Cancer Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2007
- Primary completion
- Oct 2012 (actual)
- First posted
- 26 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial is studying the side effects and best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with advanced solid 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 carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with carboplatin and paclitaxel may help kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To determine the recommended dose for phase II studies of veliparib (ABT-888 ) that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies. (Stratum I) II. To determine the recommended dose for phase II studies of veliparib that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies that harbor a germline BRCA1/2 mutation. (Stratum II) (added 04/07/09)
SECONDARY OBJECTIVES:
- To define the dose-limiting toxicity and other toxicities associated with the use of this combination.
II. To obtain preliminary evidence of antitumor activity in patients treated with this combination.
III. To evaluate the pharmacokinetic parameters of veliparib, carboplatin, and paclitaxel when administered as a combination.
IV. To conduct correlative science studies.
OUTLINE: This is a multicenter, dose-escalation study of veliparib. Patients are stratified according to BRCA status (no [stratum I] vs yes [stratum II]).
Patients receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib orally (PO) twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo peripheral blood mononuclear cell collection periodically for pharmacokinetic and biomarker studies.
After completion of study treatment, patients are followed up for 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor therapy and chemotherapy) | Experimental | Drug: Carboplatin, Other: Laboratory Biomarker Analysis, Drug: Paclitaxel, Other: Pharmacological Study, Drug: VeliparibPatients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically or cytologically confirmed advanced solid malignancy
- Patients enrolled in stratum II of the study must have BRCA1/2 mutation (added 04/07/09)
- Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment
- ECOG performance status 0-2
- Life expectancy > 12 weeks
Key exclusion criteria (15 listed)
- Known history of allergic reactions to veliparib, carboplatin, or Cremophor-paclitaxel
- Uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Psychiatric illness or social situations that would preclude compliance with study requirements
- Peripheral neuropathy > grade 1
- Inability to take oral medications on a continuous basis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Treatment (enzyme inhibitor therapy and chemotherapy) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (enzyme inhibitor therapy and chemotherapy) |
| PaclitaxelAlso: Anzatax, Asotax, Bristaxol, PraxelGiven IV | Drug | Treatment (enzyme inhibitor therapy and chemotherapy) |
| Pharmacological StudyCorrelative studies | Other | Treatment (enzyme inhibitor therapy and chemotherapy) |
| VeliparibAlso: ABT-888, PARP-1 inhibitor ABT-888Given PO | Drug | Treatment (enzyme inhibitor therapy and chemotherapy) |
Primary outcome
Recommended phase II dose (RP2D) for each stratum
Time frame: Up to 4 weeks
The RP2D for each cohort will be defined by the study separately. Standard up \& down dose-escalation scheme to determine the RP2D will be use, and toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
7 secondary outcomes
Dose-limiting toxicity (DLT)
Time frame: During course 1
Frequency of platinum-DNA adducts
Time frame: At baseline and 4 weeks post-treatment
Incidence of stable disease (SD)
Time frame: Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment
PAR levels
Time frame: Up to 4 weeks post-treatment
Responses to veliparib in combination with carboplatin and paclitaxel
Time frame: Up to 4 weeks post-treatment
Time to progression (TTP)
Time frame: Time from start of treatment to time of progression, assessed up to 4 weeks post-treatment
Toxicities as assessed by CTCAE v.4.0
Time frame: From the time of their first treatment with veliparib to up to 4 weeks post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2015.
Related trials for Adult Solid Neoplasm
Recruiting
An Exploratory Study to Evaluate Immune Determinants of the Response to Adoptive Cell Therapy (ACT) in Solid and Hematologic Tumors
Solid Tumor, Adult, Solid Tumor, Childhood
Active, not recruitingPhase 1
Advanced or Recurrent Solid Tumors Treated With SHetA2
Solid Tumor, Adult
RecruitingObservational study
NCI Childhood Cancer Data Initiative (CCDI) Led Pediatric, Adolescent, and Young Adult Rare Cancer Registry for Very Rare Solid Tumors
Very Rare Tumors, Very Rare Cancers
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 1
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
Solid Tumor, Advanced Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suresh Ramalingam principal investigator
University of Pittsburgh Cancer Institute (UPCI)
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carboplatin, Laboratory Biomarker Analysis and Paclitaxel in people with Adult Solid Neoplasm and BRCA1 Mutation Carrier, run by National Cancer Institute (NCI) at 7 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 16 inclusion and 15 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 22 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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?
Recommended phase II dose (RP2D) for each stratum (time frame: Up to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 May 2015.