Veliparib and Dinaciclib in Treating Patients With Advanced Solid Tumors

NCT01434316 | Active Not Recruiting Phase 1

• 9 other identifiers: NCI-2011-0345811-144DFCI-11-144CDR00007109008484P30CA006516R01CA090687U01CA062490UM1CA186709
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and the best dose of veliparib and dinaciclib in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment. Veliparib and dinaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose of veliparib/dinaciclib

  Will be determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Frequency tables of worst grade of adverse event, drug-related adverse events, and worst grade of laboratory value will be presented by dose cohort.

  Up to day 28

Secondary Outcomes (9)

• Pharmacokinetic parameters (maximum concentration [Cmax], area under the curve [AUC], and half-life [t1/2]) of veliparib in the absence or presence of dinaciclib

  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 cycle 1)

• Pharmacokinetic parameters (Cmax, AUC, t1/2) of dinaciclib in the presence of veliparib

  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 cycle 1)

• Changes in immunohistochemical or biochemical measurements of cyclin-dependent kinase (cdk), poly (ADP-ribose) polymerase 1 activity

  Baseline up to day 10

• Level of deoxyribonucleic acid damage in tissue samples

  Up to day 10

• Expression of homologous recombination repair proteins

  56 days

Other Outcomes (3)

• Change in parameters defining combined cdk and PARP inhibition

  Baseline up to 56 days

• Change in BRCA1 and RAD51 expression

  Baseline to day 7 of cycle 1

• Change in BRCA1 and RAD51 expression

  Baseline and within 48 hours of combination therapy in cycle 1

Study Arms (1)

Treatment (veliparib and dinaciclib)

EXPERIMENTAL

PART 1A: Patients receive veliparib PO BID on days 1-28 and dinaciclib IV over 2 hours on days 8 and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. PART 1B: Patients receive veliparib and dinaciclib as patients in Part 1A. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. PART 1C: Patients receive veliparib PO BID on days 1-7 of cycle 0. Patients then receive veliparib PO BID on days 1-21 and dinaciclib IV over 2 hours on days 1, 4, 8, and 11 or days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Dinaciclib; Drug: Veliparib

Interventions

Dinaciclib DRUG

Given IV

Also known as: CDK Inhibitor SCH 727965, MK 7965, MK-7965, MK7965, SCH 727965, SCH-727965, SCH727965

Treatment (veliparib and dinaciclib)

Veliparib DRUG

Given PO

Also known as: ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

Treatment (veliparib and dinaciclib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 PARP inhibitors is permitted in all cohorts; prior exposure to cyclin-dependent kinase inhibitors other than SCH727965 is permitted
• Absolute neutrophil count \>= 1,500/mm\^3
• Hemoglobin (Hgb) \> 10.0 g/dL with no blood transfusion in the past 28 days
• 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

You may not qualify if:

• 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; palliative radiation therapy (XRT) can be administered on study after documented discussion with the principal investigator; for patients in expansion cohorts, this must not involve target lesions
• 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
• 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 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 because ABT-888 and SCH727965 are anti-proliferative agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with ABT-888 and SCH727965, 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 CYP3A4 inhibitor or CPY3A4 inducer who cannot be changed to another medication are excluded
• Subjects with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS
• Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Interventions

dinaciclib; veliparib

Study Officials

• Geoffrey I Shapiro

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2011
• First Posted: September 14, 2011
• Study Start: November 11, 2011
• Primary Completion: March 28, 2023
• Study Completion (Estimated): August 2, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-01

Locations

US (2)