1100 Participants Needed

Treatment Timing for Non-Small Cell Lung Cancer

Recruiting at 228 trial locations
KK
Overseen ByKathryn Kelley, MPH
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Alliance for Clinical Trials in Oncology
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This phase III trial compares standard therapy given after surgery (adjuvant) to standard therapy given before and after surgery (perioperative) in treating patients with stage II-IIIB non-small cell lung cancer (NSCLC) that can be removed by surgery (resectable). The usual approach for patients with resectable NSCLC is chemotherapy and/or immunotherapy before surgery, after surgery, or both before and after surgery. This study is being done to find out which approach is better at treating patients with lung cancer. Treatment will be administered according to the current standard of care at the time of enrollment. Chemotherapy options may include cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and vinorelbine at standard doses according to the treating physician. 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. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Other chemotherapy drugs, such as vinorelbine, 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 . Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with chemotherapy and immunotherapy prior to surgery and continuing treatment after surgery may be a more effective treatment option than adjuvant therapy alone in patients with stage II-IIIB resectable NSCLC.

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 this with the trial coordinators or your doctor to get a clear answer based on your specific situation.

What data supports the effectiveness of the drugs Atezolizumab, Nivolumab, and Pembrolizumab for treating non-small cell lung cancer?

Research shows that the drugs atezolizumab, nivolumab, and pembrolizumab, which are types of immunotherapy, have been effective in treating advanced non-small cell lung cancer, helping patients live longer and improving their overall outcomes.12345

What safety data exists for treatments like Atezolizumab, Nivolumab, and Pembrolizumab in humans?

Atezolizumab, Nivolumab, and Pembrolizumab have been studied for safety in patients with non-small cell lung cancer, showing they are generally safe but can cause immune-related side effects. These treatments are approved for use because they improve survival and quality of life compared to standard chemotherapy.45678

How is the drug treatment with Atezolizumab, Nivolumab, and Pembrolizumab different for non-small cell lung cancer?

This drug treatment is unique because it uses immunotherapy, which helps the body's immune system fight cancer by targeting specific proteins (PD-1/PD-L1) on cancer cells, potentially leading to longer-term survival compared to traditional chemotherapy.3591011

Research Team

LM

Linda Martin, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

DM

Daniel Morgensztern, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

RA

Raid Aljumaily, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

This trial is for adults over 18 with stage II-IIIB resectable non-small cell lung cancer (NSCLC), who haven't had systemic treatment for NSCLC in the last 5 years. They should have a performance status indicating they can care for themselves and are up to light work. People with certain other cancers or treatments within the past 3 years, active autoimmune diseases, interstitial lung disease, transplants that conflict with immunotherapy, or untreated HIV are excluded.

Inclusion Criteria

My lung cancer is at stage IIA to IIIB and can be removed with surgery.
I haven't had systemic treatment for NSCLC in the last 5 years, except for early-stage cancer treated to cure.
I haven't been treated for another cancer within 3 years, except for early-stage cancers from which I've been disease-free for a year.
See 4 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Neoadjuvant Therapy

Patients receive platinum-based doublet chemotherapy and immune checkpoint inhibitor therapy before surgery

Up to 4 cycles
Multiple visits for chemotherapy administration

Surgery

Patients undergo surgery to remove the tumor

Within 28 days of registration
1 visit (in-person)

Adjuvant Therapy

Patients receive immune checkpoint inhibitor therapy for up to 1 year after surgery

Up to 1 year
Regular visits for therapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months for up to 10 years
Biannual visits (in-person)

Treatment Details

Interventions

  • Atezolizumab
  • Carboplatin
  • Cisplatin
  • Docetaxel
  • Gemcitabine
  • Nivolumab
  • Pembrolizumab
  • Pemetrexed
  • Vinorelbine
Trial Overview The study compares standard post-surgery therapy to therapy given both before and after surgery in patients with resectable NSCLC. It includes chemotherapy drugs like cisplatin and docetaxel, which kill or stop tumor growth; pemetrexed and gemcitabine that block DNA creation; vinorelbine that prevents cells from spreading; plus immunotherapies like nivolumab, pembrolizumab, atezolizumab which boost the immune system's attack on tumors.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)Experimental Treatment13 Interventions
NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Group II: Arm 1 (surgery, adjuvant therapy)Experimental Treatment13 Interventions
SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials
521
Recruited
224,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

A network meta-analysis of five trials showed that PD-1 inhibitors (pembrolizumab and nivolumab) had higher overall response rates (ORR) compared to the PD-L1 inhibitor (atezolizumab), particularly in patients with high PD-L1 expression.
Both pembrolizumab and nivolumab demonstrated superior overall survival (OS) benefits in various patient subgroups, but treatment decisions should also consider individual patient characteristics and safety profiles.
Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis.Almutairi, AR., Alkhatib, N., Martin, J., et al.[2019]
A meta-analysis of three randomized controlled trials involving 1,887 patients found that nivolumab and pembrolizumab have similar efficacy in treating advanced non-small-cell lung cancer, with no significant differences in overall response rates, overall survival, or progression-free survival.
However, pembrolizumab was associated with a higher incidence of severe adverse effects (grades ≥3) compared to nivolumab, indicating a potential safety concern when choosing between these two treatments.
Indirect comparison between pembrolizumab and nivolumab for the treatment of non-small cell lung cancer: A meta-analysis of randomized clinical trials.Peng, TR., Tsai, FP., Wu, TW.[2018]
A systematic review of 28 studies involving second-line treatments for non-small-cell lung cancer (NSCLC) showed that PD-L1/PD-1 inhibitors (atezolizumab, nivolumab, and pembrolizumab) have comparable and superior expected 5-year overall survival rates compared to other treatment options.
In adjusted analyses, atezolizumab was ranked as the most effective PD-L1/PD-1 inhibitor for long-term survival, followed by nivolumab and pembrolizumab, highlighting the importance of these immunotherapies in improving outcomes for patients with NSCLC.
Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies.Schulz, C., Gandara, D., Berardo, CG., et al.[2020]

References

Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis. [2019]
Indirect comparison between pembrolizumab and nivolumab for the treatment of non-small cell lung cancer: A meta-analysis of randomized clinical trials. [2018]
Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies. [2020]
Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer. [2021]
The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer. [2021]
Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis. [2019]
Immune checkpoint blockade for advanced non-small cell lung cancer: challenging clinical scenarios. [2023]
Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]
Retreatment With Anti-PD-L1 Antibody in Advanced Non-small Cell Lung Cancer Previously Treated With Anti-PD-1 Antibodies. [2019]
Time-dependent population PK models of single-agent atezolizumab in patients with cancer. [2021]
11.United Statespubmed.ncbi.nlm.nih.gov
Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2023]