Veliparib and Dinaciclib With or Without Carboplatin in Treating Patients With Advanced Solid Tumors
Status: Recruiting
Phase: Phase 1
Diagnosis: Solid Tumor/Phase I
NCT ID: NCT01434316
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 11-144
This phase I trial studies the side effects and the best dose of veliparib and dinaciclib given together with or without carboplatin and to see how well they work 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 cancer 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
Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital
Overall PI:
Geoffrey Shapiro, MD, PhD,
Dana-Farber Cancer Institute
Site-responsible Investigators:
Contacts:
Dana-Farber Cancer Institute:
Linda Pointon, 617-632-4391,
linda_pointon@dfci.harvard.edu
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of a solid tumor for which no standard or curative
therapy exists or for which standard therapy is no longer effective
- Measurable or evaluable disease
- Eligible patients in the dose-escalation phases of the trial must agree to biopsies
of normal skin, unless they undergo optional tumor biopsies and 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 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
- Patients with known active brain metastases are excluded
- Patients with a history of 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
PATIENT CHARACTERISTICS:
- See Disease Characteristics
- ECOG performance status ≤ 2
- Absolute neutrophil count ≥ 1,500/mm^3
- Hgb > 9.0 g/dL
- Platelet count ≥ 100,000/mm^3
- Total bilirubin < 1.5 mg/dL
- AST (SGOT)/ALT (SGPT) ≤ 2.5 times the institutional upper limit of normal (ULN) (for
patients with known liver metastases, AST and ALT ≤ 5 times ULN)
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- PT/INR and PTT ≤ 1.5 times ULN
- 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
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with veliparib (ABT-888) and dinaciclib (SCH727965)
- Patients must be able to swallow pills
- Patients enrolling in Part 2 are excluded if they have a known allergy to platinum
drugs (cisplatin or carboplatin)
- No 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
- No 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
- No patients with active seizure or a history of seizure
- No patients with a known allergy to lidocaine
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- 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
- 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-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 veliparib (ABT-888) or other PARP inhibitors is permitted
- Prior exposure to cyclin-dependent kinase inhibitors other than dinaciclib
(SCH727965) is permitted
- 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)
- Men receiving treatment for prostate cancer will be maintained at castrate
levels of testosterone by continuation of luteinizing-releasing hormone agonists
- No patients requiring chronic maintenance of white blood cell counts or granulocyte
counts through the use of growth factor support (e.g., Neulasta®, Neupogen®)
- No patients who have previously received SCH727965
- Patients on a potent CYP3A4 inhibitor or CPY3A4 inducer who cannot be changed to
another medication are excluded