Trial record 1 of 1 for:    NCT01434316
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Veliparib and Dinaciclib With or Without Carboplatin in Treating Patients With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01434316
First received: September 13, 2011
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

This phase I trial studies the side effects and the best dose of veliparib and dinaciclib given together with or without carboplatin in treating patients with advanced solid tumors. Veliparib and dinaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib and dinaciclib with or without carboplatin may kill more tumor cells.


Condition Intervention Phase
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Unspecified Adult Solid Tumor, Protocol Specific
Drug: veliparib
Drug: dinaciclib
Drug: carboplatin
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Trial of ABT-888 and SCH727965 Without or With Carboplatin in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Recommended phase 2 dose of veliparib/dinaciclib with or without carboplatin determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Frequency tables of worst grade of adverse event, drug-related adverse events, and worst grade of laboratory value will be presented by dose cohort.


Secondary Outcome Measures:
  • Pharmacokinetics parameters (maximum concentration [Cmax], area under the curve [AUC], and half-life [t1/2]) of veliparib in the absence or presence of dinaciclib [ Time Frame: At 0.25, 0.5, 1, 2, 2.25, 2.50, 3.0, 4.0, 6.0, 8.0, and 24.0 hours after dosing (days 1 and 8 of course 1) ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters (Cmax, AUC, t1/2) of dinaciclib in the presence of veliparib [ Time Frame: At 0.25, 0.5, 1, 2, 2.25, 2.50, 3.0, 4.0, 6.0, 8.0, and 24.0 hours after dosing (days 1 and 8 of course 1) ] [ Designated as safety issue: No ]
  • Changes in immunohistochemical or biochemical measurements of cyclin-dependent kinase (cdk), poly (ADP-ribose) polymerase 1 activity [ Time Frame: Baseline up to day 10 ] [ Designated as safety issue: No ]
    Levels of activity and percent changes post-treatment will be summarized using descriptive statistics.

  • Level of deoxribonucleic acid damage in tissue samples [ Time Frame: Up to day 10 ] [ Designated as safety issue: No ]
  • Expression of homologous recombination repair proteins [ Time Frame: 56 days ] [ Designated as safety issue: No ]
  • Anti-tumor activity of veliparib/dinaciclib with or without carboplatin as assessed by Response Evaluation Criteria In Solid Tumors 1.1 [ Time Frame: 56 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 116
Study Start Date: November 2011
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (veliparib, dinaciclib, and carboplatin)

PART 1: Patients receive veliparib PO BID on days 1-28 and dinaciclib IV over 2 hours on days 8 and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Once the MTD is determined, part 2 of study is initiated.

PART 2: Patients receive veliparib and dinaciclib as patients in part 1. Patients also receive carboplatin IV over 60 minutes on days 8 and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: veliparib
Given PO
Other Name: ABT-888
Drug: dinaciclib
Given IV
Other Names:
  • CDK inhibitor SCH 727965
  • cyclin-dependent kinase inhibitor SCH 727965
  • SCH 727965
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of ABT-888 (veliparib) and SCH727965 (dinaciclib) without or with carboplatin in patients with advanced solid tumors.

II. To determine the recommended phase 2 dose (RP2D) for ABT-888 in combination with SCH727965 without or with carboplatin, determined by evaluating the feasibility, safety, dose-limiting toxicities, and the maximally tolerated dose(s).

SECONDARY OBJECTIVES:

I. To confirm the safety of the combination of ABT-888 and SCH727965 without or with carboplatin in patients with known breast cancer (BRCA)1 or BRCA2 germline mutation.

II. To characterize the pharmacokinetic parameters of ABT-888 both alone and in combination with SCH727965 without or with carboplatin.

III. To assess the pharmacodynamic effects of ABT-888 in combination with SCH727965 without or with carboplatin, both in surrogate tissues and in tumor.

IV. To assess preliminary antitumor activity of the ABT-888/SCH727965 and ABT-888/SCH727965/carboplatin combinations in subjects with solid tumors.

OUTLINE: This is a dose-escalation study of veliparib and dinaciclib followed by an expanded BRCA-proficient and BRCA-deficient cohort study.

PART 1: Patients receive veliparib orally (PO) twice daily (BID) on days 1-28 and dinaciclib IV over 2 hours on days 8 and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Once the maximum-tolerated dose (MTD) is determined, part 2 of study is initiated.

PART 2: Patients receive veliparib and dinaciclib as patients in part 1. Patients also receive carboplatin IV over 60 minutes on days 8 and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have histologically confirmed diagnosis of a solid tumor for which no curative therapy exists
  • Participants must have measurable or evaluable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Prior chemotherapy is allowed; patients must not have received chemotherapy for 3 weeks prior to the initiation of study treatment and must have full recovery from any acute effects of any prior chemotherapy; patients must not have had nitrosoureas or mitomycin C for 6 weeks prior to the initiation of study treatment
  • Prior exposure to approved receptor tyrosine kinase inhibitors is permitted; at least 5 half-lives must have elapsed since the completion of the kinase inhibitor and the initiation of study treatment
  • Prior radiation therapy is allowed; patients must not have received any radiation within 3 weeks prior to the initiation of study treatment; patients may not have areas of irradiated marrow exceeding 40% of bone marrow volume
  • Prior experimental (non-Food and Drug Administration [FDA] approved) therapies and immunotherapies are allowed; patients must not have received these therapies for 3 weeks prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies
  • Prior exposure to ABT888 or other poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors is permitted; prior exposure to cyclin-dependent kinase inhibitors other than SCH727965 is permitted
  • Absolute neutrophil count >= 1,500/mm^3
  • Hemoglobin (Hgb) > 9.0 g/dl
  • Platelets >= 100,000/mm^3
  • Total bilirubin < 1.5 mg/dl
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times the institutional upper limit of normal; for subjects with known liver metastases, AST and ALT =< 5 times institutional upper limit of normal
  • Creatinine =< 1.5 times institutional upper limit of normal or creatinine clearance >= 60 mL/min/1.73 m^2
  • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 times institutional upper limit of normal
  • Women of childbearing 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; additionally, if a man suspects that he has fathered a child while taking study agents, he should also inform his treating physician immediately
  • Eligible patients in the dose escalation phases of the trial must agree to biopsies of normal skin, unless they undergo optional tumor biopsies; patients enrolled to the expanded cohorts must agree to tumor sampling; patients on anticoagulation must be able to hold warfarin or low molecular weight heparin for a sufficient amount of time to make skin and tumor biopsies safe to perform; PT/INR and PTT should be =< 1.5 times the institutional upper limit of normal prior to performance of skin or tumor biopsies, with values re-checked after the eligibility screen as medically indicated
  • Patients must be able to swallow pills
  • Patients enrolling in the BRCA-deficient cohort must have a documented BRCA1 or BRCA2 germline mutation
  • All patients must agree to provide an archival tissue block or paraffin sample from archival tissue block (approximately 10 sections) for use in pharmacodynamic correlative studies; however, patients are not considered ineligible if archival tumor is not available
  • Ability to understand and the willingness to sign a written informed consent document; subjects must be willing to adhere to dose and visit schedules

Exclusion Criteria:

  • Patients must not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (i.e. megestrol acetate, bisphosphonates); in addition, men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing-releasing hormone agonists
  • Patients with known active brain metastases are excluded; patients with a history of central nervous system (CNS) metastases that have been treated must be stable with no symptoms for > 3 months after completion of that treatment and off steroid treatment, with image documentation required prior to study enrollment
  • Patients with active seizure or a history of seizure
  • Any patient requiring chronic maintenance of white blood cell counts or granulocyte counts through the use of growth factor support (e.g. Neulasta®, Neupogen®)
  • Patients who have previously received SCH727965
  • Patients enrolling in Part 2 are excluded if they have a known allergy to platinum drugs (cisplatin or carboplatin)
  • Patients with other medical conditions judged by the investigator to be clinically relevant in the setting of this study, which may include active infectious processes, intractable emesis, or chronic diarrheal disease
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ABT-888 and SCH727965; these potential risks may also apply to other agents used in this study
  • Patients with prior seizure history who have experienced a seizure within the three months prior to enrollment are excluded
  • Subjects with a known allergy to lidocaine
  • Subjects on a potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitor or CPY3A4 inducer who cannot be changed to another medication are excluded
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01434316

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Scott J. Rodig    617-525-7825    srodig@partners.org   
Principal Investigator: Scott J. Rodig         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Geoffrey I. Shapiro    617-632-4942    geoffrey_shapiro@dfci.harvard.edu   
Principal Investigator: Geoffrey I. Shapiro         
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jeffrey Supko    617-724-1970    jsupko@partners.org   
Principal Investigator: Jeffrey Supko         
Sponsors and Collaborators
Investigators
Principal Investigator: Geoffrey Shapiro Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01434316     History of Changes
Other Study ID Numbers: NCI-2011-03458, NCI-2011-03458, CDR0000710900, DFCI-11-144, 11-144, 8484, R01CA090687, P30CA006516, U01CA062490
Study First Received: September 13, 2011
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Carboplatin
Cyclin-Dependent Kinase Inhibitor Proteins
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014