Veliparib + Dinaciclib for Advanced Cancers

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Active brain metastases, Seizure history, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest and most effective dose of two drugs, veliparib and dinaciclib, for treating advanced solid tumors that have spread and resist current treatments. These drugs block enzymes that promote cancer cell growth. It suits individuals with solid tumors lacking curative options and who have not received cancer treatment for at least three weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot receive any other anti-cancer therapy while on this study, except for certain supportive care medications. If you are on a potent CYP3A4 inhibitor or inducer, you may need to switch to another medication.

Is there any evidence suggesting that veliparib and dinaciclib are likely to be safe for humans?

Research shows that veliparib and dinaciclib are under investigation for their safety in treating advanced cancers. Veliparib has been tested with other drugs, providing some insight into its safety profile. Although specific safety data for the combination of veliparib and dinaciclib is limited, some studies have explored this pairing. These studies suggest that using both drugs might benefit patients with advanced solid tumors.

As this trial is in an early phase, scientists are still determining how well these drugs work together and what side effects they might cause. Early-phase trials primarily focus on identifying side effects and determining the optimal dose. While detailed safety information may be limited, the previous use of veliparib in other treatments offers some reassurance about its safety. Participants should discuss any concerns with the trial staff or their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Veliparib and Dinaciclib for advanced cancers because these treatments offer a novel approach by targeting specific enzymes involved in cancer cell repair and division. Veliparib is a PARP inhibitor, which blocks a protein that helps cancer cells repair their DNA, making them more vulnerable to damage. Dinaciclib, on the other hand, is a cyclin-dependent kinase inhibitor that interferes with proteins necessary for cancer cell division. This combination could potentially enhance the effectiveness of treatment compared to standard therapies, which typically target cancer cells in a less specific manner.

What evidence suggests that veliparib and dinaciclib might be an effective treatment for advanced cancers?

Research has shown that using veliparib and dinaciclib together may help treat advanced solid tumors. Veliparib stops cancer cells from repairing themselves, while dinaciclib blocks proteins that aid cancer cell growth. Early studies found that this combination can benefit patients with solid tumors. In this trial, participants will receive both veliparib and dinaciclib to evaluate their combined effect on tumor growth. Although the combination is still under study, these findings are promising. ^{1 2 4 6 7}

Who Is on the Research Team?

Geoffrey I. Shapiro

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have spread and are not curable. Participants must have a certain level of blood counts, organ function, and no recent chemotherapy or radiation. They should be able to swallow pills, may have had prior treatments but need to recover from them, agree to use contraception if they can bear children, and provide tissue samples. People with uncontrolled illnesses or who are pregnant/nursing cannot join.

Inclusion Criteria

Absolute neutrophil count >= 1,500/mm^3

Ability to understand and the willingness to sign a written informed consent document; subjects must be willing to adhere to dose and visit schedules

I haven't taken any experimental drugs or immunotherapies for the last 3 weeks.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am not pregnant or breastfeeding.

I have not had a seizure in the last three months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1A

Patients receive veliparib orally twice daily on days 1-28 and dinaciclib intravenously over 2 hours on days 8 and 22. Cycles repeat every 28 days.

28 days per cycle

Treatment Part 1B

Patients receive veliparib and dinaciclib as in Part 1A. Cycles repeat every 28 days.

28 days per cycle

Treatment Part 1C

Patients receive veliparib orally twice daily on days 1-7 of cycle 0, then veliparib on days 1-21 and dinaciclib on days 1, 4, 8, and 11 or days 1 and 8. Cycles repeat every 21 days.

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Veliparib and Dinaciclib

Trial Overview The trial is testing the combination of two drugs: Veliparib (ABT-888) and Dinaciclib (SCH727965), which might block enzymes that help tumor cells grow. It's in phase I to find out the safest dose with the least side effects for patients whose cancer has spread widely.

How Is the Trial Designed?

Group I: Treatment (veliparib and dinaciclib) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In the BROCADE3 trial, crossover treatment with veliparib after disease progression on placebo plus carboplatin/paclitaxel showed limited antitumor activity, with only 16% of patients responding, particularly those with longer platinum-free intervals (PFI ≥180 days).

BRCA reversion mutations were found in some patients and were associated with shorter treatment duration and reduced efficacy of veliparib, suggesting that these mutations may contribute to resistance against the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relevance of Platinum-free Interval and BRCA Reversion Mutations for Veliparib Monotherapy after Progression on Carboplatin/Paclitaxel for gBRCA Advanced Breast Cancer (BROCADE3 Crossover). Puhalla, SL., Diéras, V., Arun, BK., et al.[2023]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/77/13_Supplement/CT047/622285/Abstract-CT047-Phase-1-dose-escalation-study-of

Phase 1 dose-escalation study of the CDK inhibitor dinaciclib ... We conducted a Phase 1 study combining dinaciclib and veliparib in patients with advanced solid tumors who are not germline BRCA carriers.

2. withpower.com withpower.com/trial/phase-1-10-2011-5a57e

Veliparib + Dinaciclib for Advanced Cancers 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01434316

Study Details | NCT01434316 | Veliparib and Dinaciclib in ... 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10931172/

The CDK Inhibitor Dinaciclib Improves Cisplatin Response ... The CDK inhibitor Dinaciclib improves cisplatin response in nonseminomatous testicular cancer: a preclinical study.

5. researchgate.net researchgate.net/publication/318809034_Abstract_CT047_Phase_1_dose-escalation_study_of_the_CDK_inhibitor_dinaciclib_in_combination_with_the_PARP_inhibitor_veliparib_in_patients_with_advanced_solid_tumors

Abstract CT047: Phase 1 dose-escalation study of the CDK ... The combination of dinaciclib (a CDK 1, 2, 5, 9, and 12 inhibitor) with the PARP inhibitor veliparib has shown preliminary clinical benefit in patients with ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.520

Phase 3 study evaluating efficacy and safety of veliparib (V ... We present primary response data from a phase 3 randomized, placebo-controlled study (NCT02032277) evaluating the addition of V + Cb or Cb to neoadjuvant ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9296104/

PARP inhibitors as single agents and in combination therapy These data suggest pamiparib had a favorable response in patients with locally advanced/metastatic HER2 negative breast cancer with gBRCA mutations. Although ...