Nivolumab + Chemotherapy +/- Radiation for Lung Cancer (CA209-6K6 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Montefiore Medical Center
Stay on your current meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests a combination of nivolumab, chemotherapy, and sometimes targeted radiation in patients with a specific type of lung cancer that can be surgically removed. The treatment aims to shrink the tumor and kill cancer cells, making surgery more effective. Nivolumab with chemotherapy has been approved by the FDA as the first immunotherapy-based treatment for non-small cell lung cancer.
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, you cannot use immunosuppressive medication within 14 days before the first dose of nivolumab, except for certain low-dose steroids and premedication for hypersensitivity reactions. It's best to discuss your current medications with the study team.
Is the drug Nivolumab with Platinum Doublet a promising treatment for lung cancer?Yes, Nivolumab, when used as a first-line treatment for non-small cell lung cancer, has shown to improve survival. While adding platinum-doublet chemotherapy didn't further increase this effect, Nivolumab alone is promising. Additionally, combining platinum-based chemotherapy with other treatments has shown to reduce mortality and improve long-term outcomes in lung cancer patients.12589
What data supports the idea that Nivolumab + Chemotherapy +/- Radiation for Lung Cancer is an effective treatment?The available research shows that Nivolumab, when used as a first-line therapy for non-small cell lung cancer, can improve survival. However, adding some platinum-doublet chemotherapy combinations did not further increase this effect, and it may increase the treatment's side effects. This suggests that while Nivolumab is effective on its own, combining it with chemotherapy might not always enhance its benefits. Additionally, platinum-based chemotherapy, like oxaliplatin, is a standard treatment for advanced lung cancer and has shown similar effectiveness to other platinum regimens, with varying outcomes in different studies. This indicates that Nivolumab, especially when used alone, is a promising option for treating lung cancer.13478
What safety data is available for Nivolumab combined with chemotherapy and/or radiation in lung cancer treatment?The safety data for Nivolumab combined with chemotherapy, such as platinum-based doublets (cisplatin, carboplatin, oxaliplatin), indicates that while these combinations can improve survival, they may also increase toxicity. Oxaliplatin-based regimens have a more favorable toxicity profile compared to cisplatin, particularly in patients who cannot tolerate cisplatin. Studies show that oxaliplatin causes less severe leukocytopenia and neutropenia compared to cisplatin or carboplatin. However, adding chemotherapy to Nivolumab may increase the immunotherapy's toxicity. Overall, the efficacy and toxicity profiles of these combinations are similar, but individual patient tolerance and specific side effects should be considered.34678
Eligibility Criteria
Adults over 18 with resectable stage IIA to IIIB non-small cell lung cancer, who haven't had previous lung cancer treatment. They must be able to undergo radiation therapy if needed, have a good performance status (ECOG 0 or 1), and agree to use effective birth control. Excluded are those on recent immunosuppressants, with certain allergies or autoimmune diseases, active infections like TB or hepatitis B/C, pregnant/breastfeeding women, and anyone with another primary malignancy.Inclusion Criteria
I am fully active or can carry out light work.
I am older than 18 years.
My lung tumor can be treated with targeted radiation therapy.
I have not received any treatment for my lung cancer.
Exclusion Criteria
I haven't received any cancer treatment in the last 30 days.
I have another type of cancer, but it's not active.
I have a history of lung conditions like interstitial lung disease or pneumonitis.
I have previously received immunotherapy.
I have moderate to severe nerve damage.
Participant Groups
This study is testing the effectiveness of Nivolumab (an immunotherapy drug) combined with chemotherapy before surgery in patients with early-stage non-small cell lung cancer. Some participants will also receive stereotactic body radiation therapy. The goal is to see if these treatments can improve outcomes when given before tumor removal.
2Treatment groups
Experimental Treatment
Active Control
Group I: Nivolumab + Platinum Doublet Chemotherapy + SBRT (8gy x 3)Experimental Treatment3 Interventions
SBRT will be delivered near the conclusion of cycle 1 with platinum-based doublet chemotherapy (PDC) along with nivolumab for 3 cycles every 3 weeks. The intent is to deliver SBRT on three consecutive days when the concentration of radiosensitizing chemotherapy agents in the subject's system is at a minimum, to minimize toxicity risks. It is expected that some subjects may not receive SBRT on three consecutive days due to machine breakdown, inclement weather, or other logistic issues. Subjects must not receive SBRT within 72 hours after a cisplatin or carboplatin infusion
Group II: Nivolumab + Platinum Doublet ChemotherapyActive Control2 Interventions
All participants will receive platinum-based doublet chemotherapy (PDC) along with nivolumab for 3 cycles every 3 weeks. Carboplatinum (AUC=5) can be used instead of Cisplatin (75 mg/m2) from cycle 2 for Cisplatin induced neuro/oto/nephrotoxicity as long as the subject remains eligible for doublet chemotherapy. Participants with nonsquamous tumors will receive pemetrexed (500 mg/m2). Participants with squamous tumors will receive either docetaxel (75 mg/m2 on day 1) or gemcitabine (1000 mg/m2 on days 1, 8). Cycles will be every 3 weeks and a maximum of a 2 week delay will be permitted for resolution of toxicities.
Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:
🇺🇸 Approved in United States as Opdivo for:
- Advanced or metastatic gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Esophageal squamous cell carcinoma
🇪🇺 Approved in European Union as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
🇨🇦 Approved in Canada as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
🇨🇭 Approved in Switzerland as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Montefiore Medical Center-Albert Einstein College of MedicineBronx, NY
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Who is running the clinical trial?
Montefiore Medical CenterLead Sponsor
Bristol-Myers SquibbIndustry Sponsor
References
[Chemotherapy for non-small cell lung cancer]. [2018]The combination of cisplatin and either a vinca alkaloid or etoposide is one of the most effective chemotherapeutic regimens for non-small cell lung cancer. Meta-analyses of clinical trials in which cisplatin-based combination chemotherapy was compared with supportive care in patients with non-resectable non-small cell lung cancer showed that the chemotherapy reduced mortality. In the last decade, new agents, including vinorelbine, edatrexate, paclitaxel, docetaxel, irinotecan, topotecan and gemcitabine, have shown promise in the treatment of non-small cell lung cancer, and new agents combined with platinum compounds have reached the level of phase III testing. Randomized studies in which radiotherapy alone was compared with radiotherapy and cisplatin-based combination chemotherapy in patients with stage III disease showed that combined treatment can prolong survival and improve long-term outcome in patients with locally advanced non-small cell lung cancer. Recently, new agents combined with radiotherapy have been tested. Regimens in which platinum compounds are combined with new agents hold promise for more successful treatment of this disease.
Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. [2017]Combined modality therapy for non-small-cell lung cancer (NSCLC) has produced promising results. A multiinstitutional phase II clinical trial was conducted to evaluate the activity and toxicity of paclitaxel, carboplatin, and concurrent radiation therapy on patients with locally advanced NSCLC.
Efficacy and safety of oxaliplatin and docetaxel in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC). [2018]Platinum-based doublets are recommended as treatment for advanced or metastatic non-small-cell lung cancer (NSCLC); however, chemotherapy must be tailored to limit side effects. A phase II study was conducted to evaluate the efficacy and safety of oxaliplatin combined with docetaxel for NSCLC.
Oxaliplatin in first-line therapy for advanced non-small-cell lung cancer. [2020]Platinum doublets are the recommended standard first-line chemotherapy for stage IIIB/IV non-small-cell lung cancer (NSCLC). As efficacy outcomes associated with currently approved agents (cisplatin and carboplatin) are broadly similar, the decision about which platinum-based doublet to use is based on other factors such as toxicity. The goals for new platinum agents are to maintain and perhaps improve current efficacy and to improve toxicity. The aim of this article is to review the available clinical data from studies investigating the third-generation platinum analogue oxaliplatin in patients with advanced NSCLC. Information was obtained from the PubMed database and from recent presentations at national and international meetings. Oxaliplatin has been studied as monotherapy and in combination with a wide range of other chemotherapies (vinca alkaloids, taxanes, gemcitabine, and pemetrexed), mainly in phase II trials. Preliminary results from studies in which oxaliplatin-based doublets have been combined with targeted agents (eg, bevacizumab) are now available. In general, the clinical activity observed with oxaliplatin-based therapy is similar to that seen with other currently used platinum regimens, although outcomes vary between individual trials (response rates, 23%-48%; median progression-free survival, 2.7-7.3 months; median overall survival, 7.3-13.7 months). The toxicity profile of oxaliplatin, particularly when compared with cisplatin, makes it an alternative treatment, especially in patients unable to tolerate cisplatin. However, well-conducted randomized phase III trials will be needed to clarify which particular groups of patients with NSCLC may benefit from oxaliplatin-based therapy.
[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.
Oxaliplatin-Based Doublets Versus Cisplatin or Carboplatin-Based Doublets in the First-Line Treatment of Advanced Nonsmall Cell Lung Cancer. [2022]The efficacy and toxicity of oxaliplatin-based versus carboplatin/cisplatin-based doublets in patients with previously untreated nonsmall cell lung cancer (NSCLC) have been compared.We searched published randomized controlled trials of oxaliplatin-based or carboplatin/cisplatin-based medications for NSCLC. A fixed effect model was used to analyze outcomes which were expressed as the hazard ratio for overall survival (OS) and time-to-progression (TTP), relative risk, overall response rate (ORR), disease control rate (DCR), 1-year survival, and the odds ratios for toxicity were pooled.Eight studies involving 1047 patients were included. ORR tended to favor carboplatin/cisplatin but the effect was not significantly different compared with oxaliplatin doublets (P = 0.05). The effects of OS, TTP, DCR, and 1-year survival between the 2 regimens were comparable. Oxaliplatin doublets caused less grade 3/4 leukocytopenia and neutropenia. Grades 3 to 4 nonhematological toxicities and grades 3 to 4 hematological toxicities showed little difference between oxaliplatin doublets and carboplatin/cisplatin doublets.Meta-analysis shows that the efficacy of oxaliplatin doublets is similar to that of other currently used platinum doublets. The lack of significant differences in the statistic analysis does not preclude genuine differences in clinical efficacy, because higher diversities between the studies covered differences between the 2 groups in each study. Oxaliplatin combined with a third-generation agent should be considered for use as alternative chemotherapy in patients who cannot tolerate conventional platinum-based regimens because the toxicity profile is much more favorable.
Efficacy and safety of docetaxel plus oxaliplatin as a first-line chemotherapy in patients with advanced or metastatic non-small cell lung cancer. [2018]Platinum doublets are standard first-line treatment for stage IV non-small cell lung cancer (NSCLC) without targetable driver mutations. Oxaliplatin is more potent than cisplatin, requiring fewer DNA adducts to provide equivalent cytotoxicity. The objective of this study was to evaluate the efficacy and safety of oxaliplatin combined with docetaxel as a first-line treatment for stage IV NSCLC.
Nivolumab May Work as First-Line NSCLC Therapy. [2018]The first trial of nivolumab as a first-line therapy for non-small cell lung cancer suggests that the drug can improve survival. Adding some platinum-doublet chemotherapy combinations did not further increase this effect, although the median overall survival wasn't reached for paclitaxel and carboplatin. Adding chemotherapy may increase the immunotherapy's toxicity.
Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial. [2022]Nivolumab plus ipilimumab is superior to platinum-based chemotherapy in treatment-naive advanced non-small cell lung cancer (NSCLC). Nivolumab is superior to docetaxel in advanced pretreated NSCLC.