Veliparib + Chemotherapy for Advanced Cancer

Not currently recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, Antiretrovirals

Disqualifiers: Chemotherapy, Radiotherapy, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well the drug veliparib works with the chemotherapy drugs paclitaxel and carboplatin in individuals with advanced cancer that has spread or cannot be surgically removed, particularly those with liver or kidney issues. The trial aims to determine the optimal dose and assess the safety of this combination while monitoring for side effects. This trial may suit individuals with certain cancers, such as lung, ovarian, or breast cancer, that do not respond to standard treatments and who also have liver or kidney problems. Participants should not have recently undergone chemotherapy or radiation and should not have severe nerve problems. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on other investigational drugs or certain HIV medications that might interact with the trial drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining veliparib with chemotherapy can cause common side effects, such as nausea, fatigue, and myelosuppression, which means fewer blood cells are produced. One study found that an ovarian cancer patient taking veliparib with another drug experienced significant diarrhea and fatigue.

Paclitaxel, often used in cancer treatments, can lead to hair loss and peripheral neuropathy, which is a feeling of numbness or tingling in the hands or feet. It can also cause a drop in blood cells, resulting in anemia (low red blood cell count), neutropenia (low white blood cell count), and thrombocytopenia (low platelet count).

Carboplatin, another chemotherapy drug, can similarly reduce blood cell counts and may cause nausea or vomiting. These effects are common with many chemotherapy treatments.

Overall, the combination of veliparib, paclitaxel, and carboplatin has known side effects. These are generally manageable but can vary in intensity. Patients should always consult a healthcare provider about what to expect and how to manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of veliparib with carboplatin and paclitaxel for advanced cancer because of its potential to enhance treatment effectiveness. Veliparib is a PARP inhibitor, which means it works by blocking a protein that cancer cells use to repair their DNA, making them more susceptible to damage from chemotherapy. Unlike the standard treatments, which typically involve chemotherapy alone, adding veliparib could increase the cancer-killing power of the regimen. This approach targets cancer cells more precisely and could lead to better outcomes for patients with advanced cancer.

What evidence suggests that veliparib combined with chemotherapy could be effective for advanced cancer?

In this trial, participants will receive a combination of veliparib, paclitaxel, and carboplatin. Studies have shown that adding veliparib to the chemotherapy drugs carboplatin and paclitaxel can help patients with BRCA-mutated cancers live longer without their cancer worsening. Paclitaxel and carboplatin are already effective in treating various advanced cancers. In one study, 39% of patients responded well to the combination of paclitaxel and carboplatin, with some experiencing a complete response, meaning their cancer was no longer detectable. Veliparib blocks certain enzymes that allow cancer cells to grow, and adding it to chemotherapy may help kill more cancer cells. ^{5 6 7 8 9}

Who Is on the Research Team?

Hussein A Tawbi

Principal Investigator

University of Pittsburgh Cancer Institute (UPCI)

Are You a Good Fit for This Trial?

This trial is for patients with various types of advanced solid tumors that have spread or can't be surgically removed, and who also have liver or kidney dysfunction. They must not have had certain treatments before, should not be pregnant or breastfeeding, and need to use birth control. People with severe allergies to similar drugs, uncontrolled illnesses, a history of seizures, recent chemotherapy/radiotherapy, or HIV on specific therapies cannot join.

Inclusion Criteria

My kidney and liver functions vary, but are within the study's limits.

You have enough platelets in your blood (at least 100,000 per microliter).

You have enough infection-fighting white blood cells in your body.

Exclusion Criteria

You have had allergic reactions to drugs that are similar to ABT-888 or other drugs used in the study.

My brain metastases have been stable for 3 months and I'm not on steroids.

I am not pregnant and will not breastfeed if treated with ABT-888.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive veliparib orally twice daily on days 1-7 and paclitaxel and carboplatin intravenously on day 3. Treatment repeats every 21 days for 6 courses.

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Veliparib

Trial Overview The study is testing the combination of Veliparib with Paclitaxel and Carboplatin in patients with metastatic solid tumors and organ dysfunction. It aims to find the safest dose that can effectively kill tumor cells by blocking enzymes needed for cell growth while stopping them from dividing or spreading.

How Is the Trial Designed?

Group I: Treatment (veliparib, paclitaxel, carboplatin) Experimental Treatment 5 Interventions

Patients receive veliparib\* PO BID on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 3. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: \* All patients receive a single dose of veliparib PO on day -6 before course 1 (except patients with very severe renal dysfunction who receive veliparib on day -5 or -6 to coincide with a dialysis day).

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Abbott

Industry Sponsor

Trials

760

Recruited

489,000+

Dr. Etahn Korngold

Abbott

Chief Medical Officer

MD, Harvard Medical School

Robert B. Ford

Abbott

Chief Executive Officer since 2020

Bachelor's degree from Boston College, MBA from UC Berkeley, Haas School of Business

Published Research Related to This Trial

In a phase III study involving 676 patients with advanced non-small-cell lung cancer, the combination of cetuximab and taxane/carboplatin (TC) did not significantly improve progression-free survival compared to TC alone, with median PFS of 4.40 months versus 4.24 months.

However, the addition of cetuximab resulted in a significantly higher overall response rate (25.7% vs. 17.2%) and showed a trend towards improved overall survival (9.69 months vs. 8.38 months), although this did not reach statistical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. Lynch, TJ., Patel, T., Dreisbach, L., et al.[2022]

In a study involving 883 chemotherapy-naive patients with advanced-stage non-small cell lung cancer, both weekly and every-3-week schedules of paclitaxel and carboplatin showed similar efficacy in terms of response rates and survival times.

While both treatment schedules were well tolerated, the weekly schedule had a lower incidence of severe sensory neuropathy (4.4% vs. 9.1%), whereas the every-3-week schedule had a lower incidence of severe diarrhea (1.1% vs. 4.2%), highlighting the importance of considering side effects when choosing a treatment plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin. Schuette, W., Blankenburg, T., Guschall, W., et al.[2019]

In a phase II trial involving 55 patients with limited-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed promising efficacy, with 37.1% achieving a complete response and 51.4% a partial response.

The treatment was associated with moderate toxicity, primarily hematologic, but no life-threatening complications were reported, indicating that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. Gatzemeier, U., Jagos, U., Kaukel, E., et al.[2015]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9470832/

Effectiveness of paclitaxel and carboplatin combination in ... Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.01076

Carboplatin and Paclitaxel for Advanced Endometrial Cancer This was the first trial to show a survival advantage for combination chemotherapy in patients with measurable advanced or recurrent endometrial ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2778657

Efficacy and Safety of First-line Single-Agent Carboplatin ... In this randomized clinical trial of 120 vulnerable older patients with ovarian cancer, single-agent carboplatin was less feasible and active than a ...

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Carboplatin in Metastatic Castrate Resistant Prostate Cancer Initial studies of carboplatin in advanced CRPC demonstrated moderate antitumour activity but failed to show significant improvements in overall survival (OS).

5. cureus.com cureus.com/articles/205724-comparison-of-the-efficacy-of-cisplatinpaclitaxel-versus-carboplatinpaclitaxel-in-improving-survival-and-quality-of-life-in-the-advanced-ovarian-cancer-patient-population-a-systematic-review-and-meta-analysis-of-randomized-control-trials

Comparison of the Efficacy of Cisplatin/Paclitaxel Versus ... A study reported that 30% of individuals receiving carboplatin for advanced ovarian cancer experienced anemia as an adverse effect [36]. However ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/020452s005lbl.pdf

PARAPLATIN Label In two prospective, randomized controlled studies in patients with advanced ovarian cancer previously treated with chemotherapy, carboplatin achieved 6 clinical ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11157039/

pharmacologic and long-term safety data Grade 3 toxicities were diarrhea (one 5-FU patient), thrombocytopenia (two patients on carboplatin plus paclitaxel), and leukopenia (one patient on carboplatin ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/carboplatin-intravenous-route/description/drg-20062578

Carboplatin (intravenous route) - Side effects & uses Carboplatin is an antineoplastic agent (cancer medicine). It interferes with the growth of cancer cells, which are eventually destroyed by the ...

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Limitations to the use of carboplatin-based therapy in ... The safety data from OVA-301 show that trabectedin + PLD can be considered as a treatment option at any relapse of ovarian cancer, including fully platinum ...