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

Plain English Summary

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 is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Lung Adenocarcinoma, Lung Large Cell Carcinoma, Lung Non-Squamous Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8. This trial tests if adding a new drug, TRC102, to standard chemotherapy and radiation therapy improves outcomes for patients with Stage III non-squamous non-small cell lung cancer. It is for adults diagnosed with Stage IIIA, IIIB, or IIIC non-squamous non-small cell lung cancer who are candidates for aggressive treatment. Participants will receive standard chemotherapy (pemetrexed and either cisplatin or carboplatin) with radiation therapy, plus the investigational drug TRC102, followed by durvalumab. Some participants will receive standard treatment without TRC102 for comparison. Standard treatment options for this stage of lung cancer include chemotherapy, radiation therapy, and immunotherapy. This trial explores an additional drug to potentially enhance these treatments. The trial aims to enroll 42 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older and have been diagnosed with Stage IIIA, IIIB, or IIIC non-squamous non-small cell lung cancer (adenocarcinoma or large cell carcinoma). You must have measurable disease and be healthy enough to receive aggressive chemoradiotherapy. You cannot join if you have had prior radiation therapy for locally advanced lung cancer, unless it was for Stage I and does not overlap with the current treatment area. Certain other prior treatments may be allowed. Specific blood counts, organ function (kidney, liver), and performance status are required. Women of childbearing potential must have a negative pregnancy test. This trial is studying Lung Adenocarcinoma, Lung Large Cell Carcinoma, Lung Non-Squamous Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome, progression-free survival, measures how long patients live without their cancer getting worse or dying, assessed over up to 5 years. The specific primary outcome measures are: Progression free survival (PFS) (From randomization to the date of the first documented event of tumor progression or death in the absence of disease progression, assessed at 12 months from randomization and up to 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to fill a treatment gap by investigating if TRC102 can improve outcomes for patients with locally advanced non-small cell lung cancer, a group with limited treatment options. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Lung Adenocarcinoma, Lung Large Cell Carcinoma, Lung Non-Squamous Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in Stage III NSCLC, a large patient population. Success could position TRC102 as a novel addition to standard-of-care, potentially leading to a new treatmen Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific type and stage of lung cancer. Understand that you will receive standard treatments plus an experimental drug, and participation involves regular clinic visits, scans, and blood tests. Be prepared for potential side effects from chemotherapy, radiation, and the new drug, and discuss any concerns with your medical team. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 42 participants

Interventions

• 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

Primary Outcomes

• Progression free survival (PFS) (From randomization to the date of the first documented event of tumor progression or death in the absence of disease progression, assessed at 12 months from randomization and up to 5 years)

Secondary Outcomes

• Overall survival (OS) (From randomization until death from any cause, assessed up to 5 years)
• Incidence of grade 3 or higher adverse events (Up to 1 year)

Full Eligibility Criteria

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed adenocarcinoma or large cell carcinoma of the lung with confirmation by immunohistochemistry (histologic tissue diagnosis is preferred, but cytology is acceptable).
* Patients must have newly staged IIIA, IIIB or IIIC disease according to the 8th tumor, node, metastasis (TNM) staging classification and to be considered appropriate candidates for aggressive chemoradiotherapy.
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam.
* Patients must have diagnosed NSCLC, with no prior overlapping radiation therapy delivered for locally advanced NSCLC. Prior stereotactic radiation therapy for stage I lung cancer without overlapping is allowed. Prior systemic antineoplastic therapy is allowed, as deemed appropriate by the treating physician. Prior surgery is allowed. History of previous stage I NSCLC with new mediastinal nodal recurrence (new stage III are eligible).
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of TRC102 in combination with pemetrexed, cisplatin, and durvalumab in patients \< 18 years of age, children are excluded from this study.
* Body weight \> 30 kg with acceptable nutritional status based on evaluation by treating physician.
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%).
* Leukocytes \>= 3,000/mcL.
* Hemoglobin \>= 9.0 g/dL.
* Absolute neutrophil count \>= 1,500/mcL.
* Platelets \>= 150,000/mcL.
* Serum bilirubin within normal institutional limits (0 - 1.2 mg/ dl). (This will not apply to patients with confirmed Gilbert's syndrome \[persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology\], who will be allowed only in consultation with their physician.).
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 x institutional upper limit of normal (=\< 39 U/L).
* Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (=\< 52 U/L).
* Creatinine =\< 1.3 mg/dL.
* Measured creatinine clearance \>= 60 mL/min OR glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2.
* Acceptable pulmonary function as assessed by treating physician.
* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

  * Women \< 60 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  * Women \>= 60 years of age will be considered post-menopausal.
* Life expectancy \>= 12 months.
* Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:

  * They must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks.
  * They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression.

    * For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy.
  * They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of enrollment.
  * They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months.
  * HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with kno

Trial Locations

• Keck Medicine of USC Buena Park, Buena Park, California, United States
• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• City of Hope at Irvine Lennar, Irvine, California, United States
• City of Hope Antelope Valley, Lancaster, California, United States
• Los Angeles General Medical Center, Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
• USC Norris Oncology/Hematology-Newport Beach, Newport Beach, California, United States
• University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
• City of Hope South Pasadena, South Pasadena, California, United States
• City of Hope Upland, Upland, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer (NSCLC)
• Stage III Lung Cancer
• Lung Adenocarcinoma
• Lung Large Cell Carcinoma
• Chemotherapy
• Radiation Therapy
• Immunotherapy
• Antineoplastic Agents
• DNA Repair Inhibitors

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