TRC102 + Chemotherapy/Radiation for Lung Cancer

Recruiting at 25 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Brain metastases, Autoimmune disorders, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 31

Duration: 2 cycles of 21 days each, followed by up to 1 year

42 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the study team to ensure they don't interfere with the trial treatments.

What data supports the effectiveness of the treatment TRC102 + Chemotherapy/Radiation for Lung Cancer?

Research indicates that combining chemotherapy with radiation therapy is more effective than radiation alone for treating non-small cell lung cancer (NSCLC). Specifically, cisplatin, a component of the treatment, has shown improved survival rates when used with radiation therapy compared to using radiation alone. ^{1 2 3 4 5}

Is the combination of TRC102, chemotherapy, and radiation therapy safe for lung cancer patients?

The combination of pemetrexed and cisplatin with radiation therapy has been studied for lung cancer, showing acceptable safety with some side effects like skin reactions and blood cell changes. Pemetrexed can cause skin reactions when used after radiation, and both pemetrexed and cisplatin can lead to blood-related side effects such as anemia (low red blood cell count) and neutropenia (low white blood cell count). ^{1 6 7 8 9}

What makes the TRC102 + Chemotherapy/Radiation treatment for lung cancer unique?

The TRC102 + Chemotherapy/Radiation treatment for lung cancer is unique because it combines TRC102, a novel agent, with standard chemotherapy drugs like cisplatin and pemetrexed, and radiation therapy, potentially enhancing the effectiveness of the treatment by making cancer cells more sensitive to radiation and chemotherapy. ^{1 2 10 11 12}

Research Team

Afshin Dowlati

Principal Investigator

Case Western Reserve University

Eligibility Criteria

Adults (18+) with stage III non-squamous NSCLC who haven't had chemotherapy or radiotherapy for lung cancer. They must have good heart, liver, and kidney function, controlled hepatitis if present, no severe autoimmune disorders or uncontrolled illnesses, and not be pregnant. Participants need measurable disease and acceptable blood counts.

Inclusion Criteria

I weigh more than 30 kg and my doctor says my nutrition is good.

I have newly diagnosed NSCLC and haven't had radiation or systemic therapy for it. Surgery is okay.

I am HIV positive and meet specific health criteria.

Exclusion Criteria

I still have side effects from previous cancer treatments.

You have a current or past history of autoimmune or inflammatory disorders.

I have had treatment for cancer that spread to my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive methoxyamine, pemetrexed, and cisplatin or carboplatin with radiation therapy for 2 cycles, followed by durvalumab for up to 1 year

2 cycles of 21 days each, followed by up to 1 year

Daily visits for radiation therapy during cycles, bi-weekly or monthly visits for durvalumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 30 days, then every 3 months for 2 years, followed by every 6 months for an additional 3 years

Treatment Details

Interventions

• Cisplatin
• Durvalumab
• Methoxyamine
• Pemetrexed
• Radiation Therapy
• TRC102

Trial Overview The trial is testing TRC102 combined with standard chemo (pemetrexed and cisplatin) plus radiation therapy followed by durvalumab against the usual treatment alone. The goal is to see if adding TRC102 improves tumor shrinkage and survival in patients.

Participant Groups

Group I: Arm I (methoxyamine, usual care) Experimental Treatment 9 Interventions

Patients receive methoxyamine PO on day 1 of each cycle, pemetrexed 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 CT scan or MRI throughout the trial and FDG-PET/CT scan during screening and optionally on study.

Group II: Arm II (usual care) Active Control 8 Interventions

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.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 18 Japanese patients with locally advanced nonsquamous non-small-cell lung cancer (NSCLC), the recommended dose of thoracic radiotherapy (TRT) was determined to be 66 Gy when combined with pemetrexed and cisplatin, showing no dose-limiting toxicities at this level.

The treatment resulted in a partial response in 15 patients, indicating that the combination of TRT and chemotherapy is effective, while common toxicities such as neutropenia and pneumonitis were manageable and did not worsen with the increased radiation dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalation study of thoracic radiotherapy in combination with pemetrexed plus Cisplatin followed by pemetrexed consolidation therapy in Japanese patients with locally advanced nonsquamous non-small-cell lung cancer. Niho, S., Kubota, K., Nihei, K., et al.[2015]

In a phase II trial involving 48 patients with stage III non-small cell lung cancer (NSCLC), a combination of cisplatin, S-1, and thoracic radiation therapy resulted in a high partial response rate of 77%, indicating significant efficacy in treating this challenging cancer.

The treatment was generally well-tolerated, with mild toxicities; serious side effects like grade 3 febrile neutropenia and pneumonitis occurred in only 8% and 4% of patients, respectively, and no severe esophagitis was reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of cisplatin plus S-1 with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer: the Okayama Lung Cancer Study Group Trial 0501. Nogami, N., Takigawa, N., Hotta, K., et al.[2022]

Combined chemotherapy and radiation therapy is more effective than radiation therapy alone for treating unresectable non-small cell lung cancer, although the best timing for chemotherapy (concurrent vs. sequential) is still uncertain.

In patients with stage IIIa and IIIb disease, surgery after neoadjuvant chemotherapy and radiation therapy shows comparable resectability and survival rates, but the impact of surgery on overall survival remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current management of unresectable non-small cell lung cancer. Livingston, RB.[2018]

Cisplatin combined with other agents like vinblastine or etoposide shows promise as an effective pre-radiotherapy treatment for locally advanced non-small cell lung cancer (NSCLC), but optimal scheduling is still being researched.

In a study of 170 patients, concurrent chemotherapy with carboplatin and radiation led to increased toxicity, including significantly higher rates of neutropenia and thrombocytopenia, indicating that while this approach may improve treatment efficacy, it also raises safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. Bishop, JF.[2019]

In a study of 101 patients with unresectable stage IIIB non-small cell lung cancer, concurrent chemoradiotherapy using cisplatin with paclitaxel, docetaxel, or gemcitabine showed similar response rates and median survival times across all treatment groups, indicating comparable efficacy.

However, the gemcitabine group experienced a higher incidence of severe radiation esophagitis, while the docetaxel group had significantly more cases of severe leucopenia and neutropenia, highlighting differences in toxicity profiles among the treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401. Oh, IJ., Kim, KS., Kim, YC., et al.[2022]

In a randomized phase 2 trial involving 101 patients with stage IV lung adenocarcinoma, the combination of Pemetrexed and Cisplatin (Pem-Cis) showed a significantly higher one-year survival rate of 72.0% compared to 52.9% for Docetaxel and Cisplatin (Doc-Cis).

Patients receiving Pem-Cis also experienced longer progression-free survival (12.6 months) compared to those on Doc-Cis (7.5 months), indicating that Pem-Cis may be a more effective first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. Su, SF., Li, M., Geng, YC., et al.[2020]

In a study involving 9 patients with locally advanced non-small cell lung cancer (LANSCLC), the combination of pemetrexed and cisplatin with concurrent late course accelerated hyperfractionated intensity modulated radiotherapy (LCAF IMRT) was found to be well tolerated, with only mild toxicity and a maximum tolerated dose not reached, establishing a recommended dose of 500 mg/m² for future studies.

The treatment showed promising efficacy, with a response rate of 66.7% and a complete remission rate of 33.3%, indicating that this combination therapy could be a viable option for patients with LANSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced non-small cell lung cancer. Li, BS., Gong, HY., Huang, W., et al.[2018]

This case report highlights the occurrence of radiation recall dermatitis in a patient with malignant pleural mesothelioma after receiving pemetrexed chemotherapy, 19 days post-radiation therapy, indicating a potential interaction between the two treatments.

Pemetrexed may act as a radiosensitizing agent, suggesting that it should be used cautiously in patients who have recently undergone radiotherapy, as it can lead to skin toxicity even after proper premedication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation recall dermatitis with pemetrexed. Hureaux, J., Le Guen, Y., Tuchais, C., et al.[2015]

In a study of 903 patients with malignant pleural mesothelioma (MPM), pemetrexed combined with cisplatin was found to be generally well tolerated, with a low treatment-associated death rate of 0.8% and an interstitial lung disease (ILD) incidence of 0.9%.

The overall response rate to treatment was 25%, and the six-month survival rate was estimated at 75.9%, indicating that pemetrexed is effective in managing MPM, consistent with previous clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. Kuribayashi, K., Voss, S., Nishiuma, S., et al.[2015]

In a study of 35 patients with unresectable stage IIIA or IIIB non-small-cell lung cancer (NSCLC), the combination of nedaplatin and irinotecan with concurrent thoracic radiotherapy resulted in a high overall response rate of 94.3%.

The treatment was found to be safe, with manageable adverse effects; serious complications like grade 3 pneumonitis or oesophagitis were absent, and there were no treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of nedaplatin and irinotecan with concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. Oshita, F., Ohe, M., Honda, T., et al.[2021]

Concurrent chemotherapy with radiotherapy has been shown to improve overall survival in various solid tumors, particularly with platinum-containing regimens like cisplatin and carboplatin.

The article focuses on the effectiveness of platinum-based chemotherapy combined with radiotherapy specifically for squamous-cell carcinomas of the head and neck and esophageal carcinomas, highlighting the need for ongoing research to determine the optimal treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum-based concurrent chemoradiotherapy for tumors of the head and neck and the esophagus. Hao, D., Ritter, MA., Oliver, T., et al.[2005]

Combined modality therapy, particularly the concurrent use of chemotherapy (cisplatin/etoposide) with chest and brain irradiation, has shown promising results in limited-stage small cell lung cancer, achieving 2-year survival rates around 40% and 5-year survival rates exceeding 20%.

In non-small cell lung cancer, sequential platinum-based chemotherapy followed by chest irradiation has improved long-term survival rates from 5-10% to 15-20%, indicating that combining treatments can significantly enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modality therapy of lung cancer. Livingston, RB.[2004]

References

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

Dose-escalation study of thoracic radiotherapy in combination with pemetrexed plus Cisplatin followed by pemetrexed consolidation therapy in Japanese patients with locally advanced nonsquamous non-small-cell lung cancer. [2015]

2. Ireland pubmed.ncbi.nlm.nih.gov

A phase II study of cisplatin plus S-1 with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer: the Okayama Lung Cancer Study Group Trial 0501. [2022]

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

Current management of unresectable non-small cell lung cancer. [2018]

4. Ireland pubmed.ncbi.nlm.nih.gov

Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401. [2022]

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

Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. [2020]

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

Phase I study of pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced non-small cell lung cancer. [2018]

8. Ireland pubmed.ncbi.nlm.nih.gov

Radiation recall dermatitis with pemetrexed. [2015]

9. Ireland pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. [2015]

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

Phase II study of nedaplatin and irinotecan with concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. [2021]

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

Platinum-based concurrent chemoradiotherapy for tumors of the head and neck and the esophagus. [2005]

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

Combined modality therapy of lung cancer. [2004]