Veliparib + Chemoradiation for Advanced Non-Small Cell Lung Cancer

Recruiting at 268 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antiretrovirals

Disqualifiers: Brain metastases, Prior systemic therapy, others

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

Compensation: Varies

Number of Visits: Unknown

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I/II partially randomized trial studies the side effects and best dose of veliparib when given together with radiation therapy, carboplatin, and paclitaxel and to see how well it works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. It is not yet known whether radiation therapy, carboplatin, and paclitaxel are more effective with or without veliparib in treating non-small cell lung cancer.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that patients must not have received any prior systemic therapy for lung cancer and may not be planning to receive any other investigational agents.

Is the combination of Veliparib, Paclitaxel, Carboplatin, and 3D-CRT safe for treating advanced non-small cell lung cancer?

Studies have evaluated the safety of Paclitaxel and Carboplatin with 3D-CRT for non-small cell lung cancer, noting both acute (short-term) and late (long-term) side effects. These treatments are generally considered safe, but they can cause side effects, which are closely monitored during trials. ^{1 2 3 4 5}

What makes the Veliparib + Chemoradiation treatment unique for advanced non-small cell lung cancer?

This treatment is unique because it combines Veliparib, a drug that may enhance the effectiveness of chemotherapy and radiation, with 3D conformal radiation therapy and the chemotherapy drugs carboplatin and paclitaxel, which are already known to work well together in treating non-small cell lung cancer. ^{1 2 6 7 8}

What data supports the effectiveness of the treatment Veliparib + Chemoradiation for Advanced Non-Small Cell Lung Cancer?

Research shows that combining chemotherapy drugs like paclitaxel and carboplatin with three-dimensional conformal radiation therapy (3D-CRT) has improved outcomes for patients with advanced non-small cell lung cancer, suggesting that this combination can be effective in managing the disease. ^{1 2 9 10 11}

Who Is on the Research Team?

Athanassios (Ethan) Argiris

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with stage III non-small cell lung cancer that can't be surgically removed. They must have certain lung function, not be pregnant or breastfeeding, able to swallow pills, and have no history of seizures or other cancers (with some exceptions). Participants need normal liver and kidney function tests, a performance status showing they're mostly active and capable, and cannot have had prior treatments for lung cancer.

Inclusion Criteria

Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method

I have been diagnosed with a specific type of advanced lung cancer that cannot be surgically removed.

You need to have evidence of a disease that can be seen on CT, MRI, or PET/CT scans.

Exclusion Criteria

Patients must not have any known immune deficiencies

I do not have cancer that has spread to my brain.

I have not had chemotherapy or biological therapy for lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients undergo 3-dimensional conformal radiation therapy once daily, 5 days a week, for 6 weeks. They also receive veliparib orally twice daily and carboplatin and paclitaxel intravenously on specified days.

6 weeks

Daily visits for radiation therapy, multiple visits for chemotherapy

Consolidation Therapy

Patients receive veliparib orally and carboplatin and paclitaxel intravenously. Treatment repeats every 21 days for 2 courses.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 4 months for the first 2 years, then every 6 months until 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Carboplatin
• Paclitaxel
• Veliparib

Trial Overview The study is testing the effectiveness of veliparib combined with radiation therapy and chemotherapy drugs carboplatin and paclitaxel versus these treatments without veliparib. It's looking at how well patients respond to this combination treatment in terms of tumor growth control. The trial will also determine the best dose of veliparib when used in this way.

How Is the Trial Designed?

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

Patients undergo 3D-CRT and receive veliparib, carboplatin, and paclitaxel as in Phase I induction and consolidation therapy.

Group II: Arm II (3D-CRT, placebo, carboplatin, paclitaxel) Active Control 5 Interventions

Patients undergo 3D-CRT as in arm I. Patients also receive placebo PO BID on days 1-43 and carboplatin and paclitaxel as in Phase I. Within 4-6 weeks after completion of chemotherapy and radiation therapy, patients receive placebo on days 1-7 and carboplatin and paclitaxel as in Phase I.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

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 a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In a phase III trial involving 200 patients with stage III non-small cell lung cancer, the chemotherapy regimen of etoposide and cisplatin (EP) showed a significantly higher 3-year overall survival rate compared to carboplatin and paclitaxel (PC), with a difference of 15% (P = 0.024).

While EP demonstrated better overall survival, it was associated with a higher incidence of severe esophagitis (20% vs. 6.3% for PC), whereas PC had a higher rate of radiation pneumonitis (33.3% vs. 18.9% for EP), indicating a trade-off in safety profiles between the two regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Liang, J., Bi, N., Wu, S., et al.[2020]

Citations

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

[Weekly paclitaxel and carboplatin with concurrent three dimensional conformal radiotherapy for locally advanced non small cell lung cancer]. [2015]

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

Multivariate analysis of survival, local control, and time to distant metastases in patients with unresectable non-small-cell lung carcinoma treated with 3-dimensional conformal radiation therapy with or without concurrent chemotherapy. [2015]

3. China pubmed.ncbi.nlm.nih.gov

[Initial outcome of induction chemotherapy with weekly paclitaxel followed by three-dimensional conformal radiotherapy and concurrent weekly paclitaxel for stage III non-small cell lung cancer]. [2015]

4. Japan pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel and carboplatin with concurrent radiation therapy in locally advanced non-small cell lung cancer: phase I study. [2015]

5. France pubmed.ncbi.nlm.nih.gov

Feasibility of high-dose three-dimensional radiation therapy in the treatment of localised non-small-cell lung cancer. [2022]

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

Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer. [2013]

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

Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified Phase I trial. [2015]

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

Toxicity and outcome of a phase II trial of taxane-based neoadjuvant chemotherapy and 3-dimensional, conformal, accelerated radiotherapy in locally advanced nonsmall cell lung cancer. [2015]

9. China pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. [2010]

10. England pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. [2020]

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

The current state of paclitaxel and radiation in the combined-modality therapy of non-small cell lung cancer. [2019]