Veliparib + Dinaciclib for Advanced Cancers

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

121 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 the combination of Veliparib and Dinaciclib safe for humans?

Veliparib has been studied in combination with other drugs like carboplatin and gemcitabine in various cancers, and these studies aimed to find the safest dose and identify any serious side effects. While specific safety data for Veliparib combined with Dinaciclib isn't provided, Veliparib has been evaluated for safety in other combinations, suggesting it has been considered safe enough to test in humans. ^{1 2 3 4 5}

What makes the drug combination of Veliparib and Dinaciclib unique for treating advanced cancers?

The combination of Veliparib and Dinaciclib is unique because Veliparib is a PARP inhibitor that helps prevent cancer cells from repairing their DNA, making them more sensitive to treatment, while Dinaciclib is a cyclin-dependent kinase inhibitor that disrupts cancer cell division. This dual approach targets cancer cells in two different ways, which may enhance treatment effectiveness compared to using either drug alone. ^{1 6 7 8 9}

Research Team

Geoffrey I. Shapiro

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Smoking History Predicts Sensitivity to PARP Inhibitor Veliparib in Patients with Advanced Non-Small Cell Lung Cancer. [2018]

3. United States 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). [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of veliparib plus carboplatin/paclitaxel in patients with HER2-negative metastatic or locally advanced breast cancer: subgroup analyses by germline BRCA1/2 mutations and hormone receptor status from the phase-3 BROCADE3 trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Veliparib for the treatment of solid malignancies. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 study of veliparib (ABT-888), a poly (ADP-ribose) polymerase inhibitor, with carboplatin and paclitaxel in advanced solid malignancies. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial. [2023]