High-Dose Radiation + Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+401 other locations
Overseen ByCharles B Simone
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: NRG Oncology
Disqualifiers: Prior radiotherapy, Pregnancy, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests whether adding a precise form of radiation therapy to the usual treatment improves outcomes for patients with advanced lung cancer that can't be operated on. The goal is to see if this combination helps patients live longer and prevents cancer from worsening. This form of radiation therapy has shown promise in improving survival rates in patients with various stages of lung cancer.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific situation with the trial coordinators or your doctor.
What data supports the effectiveness of this treatment for non-small cell lung cancer?
Research shows that combining chemotherapy drugs like paclitaxel and carboplatin with radiation therapy can improve survival rates in patients with advanced non-small cell lung cancer. Studies have demonstrated that these combinations, when used with radiation, offer better outcomes compared to radiation alone.
12345Is the combination of high-dose radiation, chemotherapy, and immunotherapy generally safe for humans?
Research shows that combinations of chemotherapy drugs like paclitaxel, carboplatin, and pemetrexed with radiation therapy have been studied for safety in treating non-small cell lung cancer and other cancers. These studies generally found that the treatments were safe, with manageable side effects, although some patients experienced severe side effects like anemia (low red blood cell count) and neutropenia (low white blood cell count).
23467What makes the High-Dose Radiation + Chemotherapy and Immunotherapy treatment unique for non-small cell lung cancer?
This treatment is unique because it combines high-dose radiation with chemotherapy and immunotherapy, using a mix of drugs like carboplatin, cisplatin, and durvalumab, which may enhance the body's immune response against cancer. The combination aims to improve local and systemic control of the disease, potentially offering better outcomes than standard chemotherapy and radiation alone.
12389Eligibility Criteria
Adults aged 18+ with stage II or III non-small cell lung cancer (NSCLC) that can't be surgically removed, but haven't had extensive prior treatment. They must have a performance status indicating they're still fairly active and able to care for themselves. Participants need functioning organs, no serious concurrent illnesses, and if of childbearing potential, agree to use contraception.Inclusion Criteria
My cancer has spread to at least one lymph node.
Your kidneys should be working well enough to filter at least 25 milliliters of waste from your blood every minute.
My doctors believe a combined treatment could potentially cure my cancer.
+11 more
Exclusion Criteria
I am not pregnant and not nursing.
I do not have cancer that started in an unknown place with a swollen lymph node.
I am willing to use effective birth control during and after my treatment as required.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive stereotactic body radiation therapy (SBRT) or conventional image guided radiation therapy (IGRT) with concurrent chemotherapy, followed by consolidation immunotherapy with durvalumab or osimertinib.
Up to 1 year
Weekly visits during radiotherapy, bi-weekly or monthly visits during immunotherapy
Follow-up
Participants are monitored for safety and effectiveness after treatment, including CT and/or PET/CT scans.
8 years
Every 3 months for 1 year, every 6 months for years 2 and 3, then yearly
Participant Groups
The trial is testing whether adding high-dose targeted radiation (SBRT) to the usual combination of image-guided radiation therapy (IGRT), chemotherapy drugs like cisplatin or carboplatin with paclitaxel, pemetrexed or etoposide, followed by immunotherapy drug durvalumab improves outcomes in inoperable NSCLC compared to standard treatment alone.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (SBRT, image guided RT, chemotherapy, immunotherapy)Experimental Treatment12 Interventions
Patients undergo SBRT and conventional IGRT and receive standard-of-care chemotherapy consisting of paclitaxel IV followed by carboplatin IV Q7D during radiotherapy or pemetrexed IV followed by carboplatin IV every 21 days during radiotherapy or etoposide IV on days 1 to 5 and days 29 to 33 followed by cisplatin IV on days 1, 8, 29, and 36 or pemetrexed IV followed by cisplatin IV every 21 days during radiotherapy. Patients then receive consolidation durvalumab IV every 2 or 4 weeks for up to one year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT during follow-up.
Group II: Arm I (image guided RT, chemotherapy, immunotherapy)Active Control11 Interventions
Patients undergo conventional IGRT and receive usual care chemotherapy consisting of paclitaxel IV followed by carboplatin IV Q7D during radiotherapy or pemetrexed IV followed by carboplatin IV every 21 days during radiotherapy or etoposide IV on days 1 to 5 and days 29 to 33 followed by cisplatin IV on days 1, 8, 29, and 36 or pemetrexed IV followed by cisplatin IV every 21 days during radiotherapy. Patients then receive consolidation durvalumab IV every 2 or 4 weeks for up to one year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT during follow-up.
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Carolinas Medical Center/Levine Cancer InstituteCharlotte, NC
Nebraska Methodist HospitalOmaha, NE
Oncology Associates PCOmaha, NE
Grant Medical CenterColumbus, OH
More Trial Locations
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Who Is Running the Clinical Trial?
NRG OncologyLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. [2015]Combined chemotherapy and thoracic radiation therapy has emerged as a primary treatment option for locally advanced, unresectable non-small cell lung cancer (NSCLC). Randomized trials and subsequent metaanalyses have shown a clear survival benefit with platinum-based combination chemotherapy administered sequentially or concurrently with hyperfractionated thoracic radiation over radiation alone. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin recently have been evaluated in numerous phase 1/11 trials at various doses in both sequential and concurrent schedules with thoracic radiation in patients with locally advanced and unresectable NSCLC. The patterns of failure in patients treated with concurrent paclitaxel/carboplatin and thoracic radiation suggest the need for additional chemotherapy either at the front end or after completion of the concurrent regimen. A large multicenter randomized study (Locally Advanced Multimodality Protocol) has been initiated to address these issues of improvement in distant control and to further refine the combined-modality approach for patients with locally advanced NSCLC. Several other combined-modality regimens incorporating a platinum compound and a novel agent like gemcitabine, vinorelbine, paclitaxel, or docetaxel have been recently completed or are in progress. The hope for the immediate future is to define an "effective" and "optimal" regimen that can be given simultaneously with thoracic radiation and can result in improved local and systemic control in patients with regionally advanced NSCLC. Numerous phase II and III trials are currently planned or under way to further define the efficacy of this novel combination of paclitaxel/carboplatin in combined-modality programs in an attempt to determine the optimal administration sequence of chemotherapy and thoracic radiation. These combined-modality programs are now being integrated into trials for early stage, potentially resectable disease. Thus, NSCLC is in fact a systemic disease requiring a multidisciplinary approach for optimal management.
[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]Based on superior results with combined-modality therapy in patients with advanced,unresectable non-small cell lung cancer (NSCLC),to evaluate the activity and toxicity of combination of paclitaxel with carboplatin and concurrent radiation therapy.
Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. [2021]This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC).
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.
An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. [2021]Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin.
Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E. [2021]This brief report describes a planned, interim, 6-patient toxicity analysis that confirms the safety of pemetrexed, carboplatin, radiation with subsequent surgery, as prescribed in the North Central Cancer Treatment Group trial N044E, in patients with locally advanced esophageal cancer.
Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]The novel multitargeted antimetabolite pemetrexed (Alimta), recently approved by the US Food and Drug Administration for the treatment of mesothelioma when combined with cisplatin, is also active in first- and second-line non-small-cell lung cancer (NSCLC). In a phase III trial comparing single-agent pemetrexed vs docetaxel (Taxotere) as second-line therapy in advanced NSCLC, survival was shown to be comparable between these agents, but side effects were significantly less frequent and severe for patients who received pemetrexed. In the frontline setting, phase II studies have shown significant activity and a very favorable toxicity profile of the combination of pemetrexed with a platinum agent. Pemetrexed has been well tolerated at systemic doses as a radiosensitizer when given as concurrent chest radiation, and a phase I study is under way to assess its tolerability in combination with carboplatin (Paraplatin) in this setting. Pemetrexed is an important addition to the armamentarium of medicines used to treat thoracic malignancies, and merits study in combination with other drugs having novel mechanisms of action.
Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. [2015]Combination chemotherapy plus radiation therapy for non-small cell lung cancer has several theoretical advantages: the potential of chemotherapy to radiosensitize tumors, the possibility of improved local control due to combined treatment, and the opportunity for spatial cooperation, attacking disease both locally and systemically and thus potentially increasing response and, ultimately, survival. The combination of radiotherapy plus standard chemotherapy (etoposide plus cisplatin) has yielded limited success; therefore, new and novel chemotherapies have been sought. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the prototype of a novel class of drugs, the taxanes, has proven feasible both alone and with other agents in combined-modality regimens with radiation. Concurrent paclitaxel/carboplatin/radiotherapy appears to offer a relatively safe and more active regimen to control local and metastatic non-small cell lung cancer than the current standard. This report reviews the range of experience with paclitaxel-based combined-modality therapy.
Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117. [2021]Phase I of Radiation Therapy Oncology Group (RTOG) 0117 determined that 74 Gy was the maximum-tolerated dose with concurrent weekly carboplatin/paclitaxel chemotherapy for inoperable non-small-cell lung cancer (NSCLC). Phase II results are reported here. PATIENTS AND METHODS Patients with unresectable stages I-III NSCLC were eligible. Chemotherapy consisted of weekly paclitaxel at 50 mg/m(2) and carboplatin at area under the curve 2 mg/m(2). The radiation dose was 74 Gy given in 37 fractions. Radiation therapy volumes included those of the gross tumor and involved nodes. The volume of lung at or exceeding 20 Gy (V20) was mandated to be