TRC102 + Chemotherapy/Radiation for Lung Cancer
Recruiting in Palo Alto (17 mi)
+21 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Investigational agents
Disqualifiers: Brain metastases, Autoimmune disorders, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
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 DNA and may kill cancer 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 cancer cells. Chemotherapy drugs, such as cisplatin, 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. 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 cancer 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.
12345Is 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).
16789What 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.
12101112Eligibility 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.
+21 more
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.
+9 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (methoxyamine, usual care)Experimental Treatment9 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 Control8 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
MetroHealth Medical CenterCleveland, OH
Newark Beth Israel Medical CenterNewark, NJ
Montefiore Medical Center-Einstein CampusBronx, NY
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
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]Pemetrexed has radiosensitizing potential when evaluated in vitro in combination with platinum-containing compounds and radiation. We determined the recommended dose (RD) of thoracic radiotherapy (TRT) with a concurrent chemotherapy combination of pemetrexed and cisplatin in Japanese patients with nonsquamous non-small-cell lung cancer (NSCLC).
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]Although cisplatin-based chemotherapy combined with thoracic irradiation (TRT) is a standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC), this treatment outcome has remained unsatisfactory. We had previously conducted a phase I trial of cisplatin plus S-1, an oral 5-fluorouracil derivative, and TRT, which were safe and effective.
Current management of unresectable non-small cell lung cancer. [2018]Historically, the standard treatment for unresectable non-small cell lung cancer was radiation therapy. Data are now accumulating, however, to indicate that combined chemotherapy and radiation therapy is superior to radiation therapy alone, although it remains uncertain whether concurrent chemotherapy with radiation therapy yields better results than a sequential approach. It is clear that surgical resection is feasible in most patients following neoadjuvant chemotherapy with or without radiation therapy, but whether surgery contributes to survival has not been established; a randomized intergroup study in stage IIIa (N2) disease addresses this question. The Southwest Oncology Group reports comparable resectability rates and survival in patients with stage IIIa and IIIb disease who received concurrent chemotherapy and radiation therapy followed by resection. Stage IV disease has traditionally been managed by supportive care alone and chemotherapy. In selected patients, statistically significant effects on survival have been seen in five randomized trials of platinum-based chemotherapy, one of which had a control arm of supportive care alone. As single agents, only carboplatin and vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) have demonstrated a survival advantage over other regimens in randomized trials, although cisplatin appears to produce similar results. Data from French studies indicate that cisplatin plus vinorelbine is superior to vindesine plus cisplatin and to vinorelbine alone. Several agents appear interesting on the basis of reported response rates in phase II trials: these include paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ), docetaxel (Taxotere; Rhoône-Poulenc Rorer, Collegeville, PA), irinotecan (CPT-II), edatrexate, and gemcitabine. Response rates are notoriously variable in this disease, however, and correlate poorly with survival effects. Randomized trials are needed to determine the value of these new agents.
Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. [2019]In scheduling chemotherapy and radiotherapy for locally advanced non-small cell lung cancer (NSCLC), chemotherapy can be given pre-radiotherapy or concurrently as a single agent or in combination. Optimal scheduling has yet to be established. Optimal pre-radiotherapy for NSCLC requires further development but cisplatin with vinblastine, vindesine, etoposide or navelbine appear the best currently available. A number of new drugs show potential for enhancing radiation effects. Concurrent chemotherapy and radiotherapy has been tested in a number of experimental tumours in cell culture. In these systems cisplatin, carboplatin, 5-fluorouracil, mitomycin-C and other agents appear to improve cell kill compared to chemotherapy alone. Mouse xenograft models allow the study of various concurrent drug and radiation schedules including the effect of radiation with cisplatin, carboplatin, paclitaxel and gemcitabine. In these systems, cisplatin in divided doses shows optimal enhancement with fractionated radiotherapy. There are a number of drug candidates for concurrent chemotherapy and radiotherapy programs. Clinical studies in head and neck cancer, esophageal cancer, small cell lung cancer and NSCLC show promising results with concurrent chemotherapy and radiotherapy. Cisplatin given daily with radiotherapy improved survival in NSCLC compared to cisplatin given weekly with radiotherapy or to radiotherapy alone. To study the toxicity of radiation and concurrent carboplatin, we have studied 170 patients with unresectable locally advanced NSCLC in a 4-arm randomized trial. An analysis of the first 100 patients entered revealed significantly more neutropenia (P
A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401. [2022]Concurrent chemoradiotherapy (CCRT) is recommended for the management of patients with unresectable non-small cell lung cancer (NSCLC). This prospective study aimed to compare the efficacy of concurrently delivered cisplatin doublets with paclitaxel, or docetaxel, or gemcitabine.
Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. [2020]Systemic chemotherapy is the standard treatment modality for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status. Recent years, there is increasing evidence showed that selected patients with stage IV disease could benefit from aggressive thoracic radiotherapy. Either pemetrexed or docetaxel, combined with cisplatin, can be used for patients with stage IV lung adenocarcinoma. However, no prospective trials have confirmed that Pem-Cis was superior to Doc-Cis in lung adenocarcinoma. In this randomized phase 2 trial, we evaluated survival outcomes, and toxicity of Pemetrexed-Cisplatin (arm A) or Docetaxel-Cisplatin (arm B) with concurrent IMRT to the primary tumor for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status. Totally, 101 patients were randomly assigned (50 in arm A and 51 in arm B). Using an intention-to-treat analysis, one-year survival rates were 72.0% and 52.9%, respectively (P=0.020). Progression-free survival was also significantly improved in the arm A (median, 12.6 v 7.5 months, P=0.013). The incidence and severity of acute pneumonitis and esophagitis was similar between two arms. Although more of grade 3 or 4 anemia and thrombocytopenia in arm A, and higher rates grade 3 or 4 neutropenia, and leukopenia were observed in arm B. Pem-Cis first-line chemotherapy with concurrent radiation therapy for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status represents a potential treatment option with acceptable toxicity and high overall survival rates.
Phase I study of pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced non-small cell lung cancer. [2018]Concurrent chemoradiotherapy in well-selected locally advanced non-small cell lung cancer (LANSCLC) is considered as standard therapy. However, the choice of anticancer agents is still unresolved. Our objectives were to determine the maximum tolerated dose and recommended dose of pemetrexed in combination with cisplatin, with concurrent late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) in patients with LANSCLC and to investigate the safety and efficacy.
Radiation recall dermatitis with pemetrexed. [2015]Pemetrexed has recently been approved for use in combination with cisplatin as first-line chemotherapy for malignant pleural mesothelioma (MPM). Radiation therapy is frequently administered to the thoracic orifices and no data are available about the interactions between radiotherapy and pemetrexed. We report the first case of radiation recall dermatitis occurring after pemetrexed chemotherapy in a patient with MPM previously treated with radiation therapy to the thoracoscopy and drainage orifices. The patient received chemotherapy with pemetrexed and cisplatin 19 days after completion of chest wall radiation therapy delivering 21 gray in 3 days. Conventional premedication by folic acid and intramuscular administration of Vitamin B12 and prednisolone was correctly performed. Twelve days later, confluent erythematous and pruritus rash of the irradiated skin was observed. The toxicity grade of this lesion was evaluated at 2 according to the Acute Radiation Morbidity Scoring Criteria proposed by the Radiation Therapy Oncology Group. Pemetrexed challenge was performed without worsening of skin lesions. Three weeks later, skin cicatrisation was observed after a desquamative phase. Persistent hyperpigmentation was seen in the irradiated skin. Pemetrexed could also act as a radiosensitizing agent that should be used with care for several weeks after radiotherapy.
Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. [2015]Pemetrexed in combination with cisplatin (Pem/Cis) is the only approved chemotherapeutic regimen for malignant pleural mesothelioma (MPM). At the time of launch, limited safety information was available. The purpose of this postmarketing all-case registry study was to investigate the safety and effectiveness of pemetrexed in patients with MPM.
Phase II study of nedaplatin and irinotecan with concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. [2021]Current international guidelines recommend the use of platinum-based chemotherapy with thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (NSCLC).
Platinum-based concurrent chemoradiotherapy for tumors of the head and neck and the esophagus. [2005]The addition of concurrent chemotherapy (CT) to standard radiotherapy (RT) for locoregional treatment has been established to improve overall survival in a variety of solid tumors. Among the many CT regimens evaluated in combination with RT in randomized controlled clinical trials and summarized in meta-analyses, platinum-containing regimens have consistently shown a survival benefit across tumor types. Cisplatin and carboplatin have been studied both as single agents and in combination with other cytotoxic drugs, concurrently with RT, but the optimal platinum-based regimen to be combined with RT continues to be explored with further investigation. In this article, the role of platinum-based CT as part of concurrent CT/RT will be discussed using 2 tumor sites in the aerodigestive tract as a paradigm: squamous-cell carcinomas of the head and neck and esophageal carcinomas. For each tumor type, we will review the state of the evidence and comment on the current state of practice and on future directions for clinical research in combined modality CT/RT.
Combined modality therapy of lung cancer. [2004]Combined modality therapy for lung cancer was first demonstrated to be successful in limited-stage small cell lung cancer. Concurrent administration of chemotherapy with chest and elective brain irradiation appears to produce the best results, with cisplatin/etoposide as the core chemotherapy. Using such programs, 2-year survival in the 40% range and 5-year survivals in excess of 20% may be expected, based on the results of multiple studies. Attempts to improve on these results through the use of altered schemes of chest irradiation or the delivery of high-dose consolidation chemotherapy are ongoing but to date have not been shown to affect survival significantly. We remain at a plateau in the effectiveness of combined modality therapy for small cell lung cancer, with little evidence that it impacts survival at all in extensive-stage disease. The incorporation of new agents in combination chemotherapy regimens, more "specific" immunotherapy directed at tumor-associated antigens, and the potential adjunctive use of broad-spectrum neuropeptide antagonists offer promise for the future. In non-small cell lung cancer, the sequential use of platinum-based chemotherapy and chest irradiation appears superior in survival to standard, daily fractionated radiation therapy used alone, with long-term survival increased from 5-10% to 15-20%. Concurrent administration of chemotherapy with cisplatin/etoposide and chest irradiation produces 2-year survival in the range of 30%, about twice that would be expected for radiation therapy alone, but has not been compared to it in the setting of a randomized trial. Low-dose cisplatin on a daily basis has been combined as a "sensitizer" with chest irradiation, producing initial results that appeared encouraging. However, these have not been reproduced in subsequent, randomized trials. Another approach to combined modalities has been to give chemotherapy or chemotherapy/radiation therapy as induction, followed by surgical resection, with or without subsequent additional treatment. Most patients (80-85%) can be resected, with encouraging survival at 2 and 3 years in the Southwest Oncology Group experience (37 and 26%, respectively). However, toxicity is greater, and such an approach is associated with an overall mortality risk in the range of 10%. A current intergroup study attempts to define the role of surgery in this setting. The major recent development that is likely to influence the future of combined modality therapy for this disease is the advent of multiple new chemotherapeutic agents, such as the taxanes, gemcitabine, vinorelbine, and the topoisomerase-I inhibitors, which have activity in stage IV disease. The immediate challenge is how to combine these agents with platinum analogues, radiation, and surgery. Aiding this process may be the use of molecular biological "markers" that may predict the chance of success or failure with a given systemic agent. The next decade is likely to see substantial improvements in the outcome of treatment for patients with stages I-III non-small cell lung cancer, based on the systemic exploration of combined modalities.