NCT05198830

Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer

A Phase 2 Randomized Study of the BER Inhibitor TRC102 in Combination With Standard Pemetrexed-Platinum-Radiation in Stage III Non-Squamous Non-Small Cell Lung Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests whether TRC102 (methoxyamine hydrochloride) in combination usual care treatment comprised of pemetrexed, cisplatin or carboplatin, and radiation therapy followed by durvalumab works better than the usual care treatment alone to shrink tumors in patients with stage III non-squamous non-small cell lung cancer (NSCLC). TRC102 is in a class of drugs called antineoplastic agents. It blocks the ability of a cell to repair damage to its deoxyribonucleic acid (DNA) and may kill tumor cells. It may also help some anticancer drugs work better. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy sources to kill tumor cells and shrink tumors. Giving TRC102 in combination with usual care treatment may be more effective than usual care treatment alone in stabilizing and lengthening survival time in patients with stage III non-squamous NSCLC.

Detailed description

PRIMARY OBJECTIVE: I. To improve progression-free survival (PFS) from 56% with current standard of care (chemoradiation followed by consolidative durvalumab) to 75% at one year with the proposed combination followed by consolidative durvalumab. SECONDARY OBJECTIVES: I. To determine overall survival with the proposed combination therapy. II. To assess the incidence of grade 3 or higher pneumonitis and other toxicities. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive methoxyamine orally (PO) on day 1 of each cycle, pemetrexed intravenously (IV) over 10 minutes on day 1 of each cycle, and cisplatin IV over 60 minutes or carboplatin IV over 30 minutes on day 3 of each cycle. Beginning day 3, patients also undergo radiation therapy daily Monday-Friday. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after cycle 2, patients receive durvalumab IV over 60 minutes every 2 weeks or monthly for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) throughout the trial and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/CT scan during screening and optionally on study. ARM II: Patients receive pemetrexed IV over 10 minutes and cisplatin IV over 60 minutes or carboplatin IV over 30 minutes on day 1 of each cycle. Beginning day 1 of each cycle, patients also undergo radiation therapy daily Monday-Friday. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after cycle 2, patients receive durvalumab IV over 60 minutes every 2 weeks or monthly for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial and FDG-PET/CT scan during screening and optionally on study. After completion of study treatment, patients are followed up at 30 days, and then every 3 months for 2 years, followed by every 6 months for an additional 3 years.

Conditions

• Lung Adenocarcinoma
• Lung Large Cell Carcinoma
• Lung Non-Squamous Non-Small Cell Carcinoma
• Stage III Lung Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Carboplatin	Given IV
DRUG	Cisplatin	Given IV
PROCEDURE	Computed Tomography	Undergo CT and FDG-PET/CT
BIOLOGICAL	Durvalumab	Given IV
PROCEDURE	FDG-Positron Emission Tomography	Undergo FDG-PET/CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Methoxyamine	Given PO
DRUG	Pemetrexed	Given IV
RADIATION	Radiation Therapy	Undergo thoracic radiation

Timeline

• Start date: 2022-12-15
• Primary completion: 2027-06-30
• Completion: 2027-06-30
• First posted: 2022-01-20
• Last updated: 2026-04-13

Locations

34 sites across 1 country: United States

Regulatory

• FDA-regulated drug study