Veliparib + Chemotherapy for Advanced Cancer

Recruiting at 18 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

94 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Veliparib, Carboplatin, and Paclitaxel for advanced cancer?

Research shows that the combination of paclitaxel and carboplatin is effective in treating advanced non-small cell lung cancer, with studies indicating a response rate of 27.5% and modest improvements in survival rates. This suggests potential effectiveness of these drugs in treating other advanced cancers as well. ^{1 2 3 4 5}

Is the combination of Veliparib, Carboplatin, and Paclitaxel safe for humans?

The combination of Carboplatin and Paclitaxel has been studied in various cancers and is generally considered to have manageable side effects, with some patients experiencing blood-related issues like low blood cell counts and mild nausea. These treatments are usually well-tolerated, but they can cause significant side effects in some patients, such as fatigue and mild nerve pain. ^{5 6 7 8 9}

What makes the drug Veliparib combined with Carboplatin and Paclitaxel unique for treating advanced cancer?

This drug combination is unique because Veliparib, a PARP inhibitor (a type of drug that blocks an enzyme involved in DNA repair), is added to enhance the effectiveness of Carboplatin and Paclitaxel, which are standard chemotherapy drugs. This combination has shown to improve progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in various cancers, including ovarian and breast cancer, compared to chemotherapy alone. ^{10 11 12 13 14}

What is the purpose of this trial?

This phase I trial studies the side effects and the best dose of veliparib when given together with paclitaxel and carboplatin in treating patients with solid tumors that are metastatic or cannot be removed by surgery and liver or kidney dysfunction. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with paclitaxel and carboplatin may kill more tumor cells.

Research Team

Hussein A Tawbi

Principal Investigator

University of Pittsburgh Cancer Institute (UPCI)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[The clinical analysis of paclitaxel at two dose levels plus carboplatin as the first-line treatment in advanced non-small cell lung cancer]. [2021]

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

Treatment of ovarian cancer: current status. [2015]

3. United States 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. [2019]

4. United States 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. [2022]

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

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]

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

Paclitaxel (Taxol)/carboplatin combination chemotherapy in the treatment of advanced ovarian cancer. [2015]

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

Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. [2015]

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

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. [2015]

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

Use of Bevacizumab in Community Settings: Toxicity Profile and Risk of Hospitalization in Patients With Advanced Non-Small-Cell Lung Cancer. [2018]

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

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line veliparib and carboplatin-paclitaxel in patients with HER2- advanced germline BRCA+ breast cancer: Subgroup analysis of a randomised clinical trial. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics and site of action exposures of veliparib with topotecan plus carboplatin in patients with haematological malignancies. [2021]

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

Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer. [2017]

14. England pubmed.ncbi.nlm.nih.gov

Veliparib monotherapy following carboplatin/paclitaxel plus veliparib combination therapy in patients with germline BRCA-associated advanced breast cancer: results of exploratory analyses from the phase III BROCADE3 trial. [2022]