Phase 2 TaxRamPem for Patients With Metastatic or Recurrent NSCLC Who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade (TaxRamPem)
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|ClinicalTrials.gov Identifier: NCT04340882|
Recruitment Status : Recruiting
First Posted : April 10, 2020
Last Update Posted : June 11, 2020
This phase 2 trial will evaluate the safety and efficacy of combining immunotherapy with a PD-1 checkpoint inhibitor (Pembrolizumab), an anti-VEGF receptor (Ramucirumab), and a taxane chemotherapy (Docetaxel) in treating patients with non-small cell lung cancer (NSCLC) who did not respond to FDA-approved treatments with platinum-based chemotherapy given concurrently or sequentially with anti-PD1/PD-L1 immunotherapy.
Pembrolizumab helps the body's immune system to attack cancer cells and hasten their ability to grow and spread. Ramucirumab blocks new blood vessel growth to reduce tumor growth. Docetaxel works mainly by stopping cancer cells from dividing. Ramucirumab combined with docetaxel is an FDA-approved therapy for NSCLC patients after progression on platinum-based chemotherapy. It has shown to improve efficacy compared to docetaxel alone in this setting. Pembrolizumab is an FDA-approved treatment for NSCLC and can be given alone or in combination with platinum-based chemotherapy.
Investigators hypothesize that the combination of docetaxel, ramucirumab, and pembrolizumab will be safe and more effective than the current standard of care treatments (docetaxel alone or in combination with ramucirumab) in patients with metastatic or recurrent NSCLC after progression on treatment with platinum-based chemotherapy and immunotherapy, given concurrently or sequentially.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Non-Small Lung Cell Cancer Recurrent Non-Small Lung Cell Cancer Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8||Drug: Docetaxel Biological: Pembrolizumab Biological: Ramucirumab||Phase 2|
I. To determine the anti-tumor efficacy of the combination treatment using the 6-month progression free survival rate by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
I. To determine the safety profile and tolerability of docetaxel and ramucirumab in combination with pembrolizumab in patients who progressed on platinum-based chemotherapy and PD-1 or PD-L1 checkpoint inhibitor given sequentially or in combination.
II. To determine immune related adverse events of the combination docetaxel, ramucirumab, and pembrolizumab.
III. To assess the overall response rate (ORR) of the combination docetaxel, ramucirumab, and pembrolizumab.
IV. To assess the overall survival (OS) of the combination docetaxel, ramucirumab, and pembrolizumab.
I. To correlate treatment response with PD-L1 22C3 expression, STK11 and KRAS mutation status.
II. To correlate treatment response with the doublet tumor mutation burden (TMB) and PD-L1 22C3 expression.
III. To perform an immunophenotypic analysis of circulating immune cells by mass cytometry before and after treatment and end of treatment (EOT).
IV. To analyze the tumor infiltrating immune cells by single cell ribonucleic acid (RNA) sequencing coupled to mass cytometry, in paired biopsies before and after treatment.
After premedication, patients will receive docetaxel intravenously (IV) over 60 minutes, ramucirumab IV over 60 minutes, then pembrolizumab IV over 30 minutes on day 1 of each 21-day cycle. The combination will be administered until confirmed disease progression defined as progression on 2 consecutive scans at least 4 weeks apart, occurrence of severe side effects, withdrawal of consent by the patient or if in the opinion of the treating physician continuing on the study treatment is not in the best interest of the patient.
The first six patients will be evaluated for safety data. If less than 2 patients experience dose limiting toxicity, enrollment on study will continue with the efficacy assessment of the combination.
Participants who experience confirmed disease progression or start a new anticancer therapy, will move into the Survival Follow-Up Phase and should be contacted by telephone every 12 weeks (+/- 3 weeks) for 2 years, then every 6 months for next 3 years, then annually until the subject's death or until the subject is lost to follow-up up to 10 years to assess for survival status until death, withdrawal of consent, or the end of the trial, whichever occurs first.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Phase 2 with initial run-in safety|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer Who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade|
|Actual Study Start Date :||June 5, 2020|
|Estimated Primary Completion Date :||April 25, 2022|
|Estimated Study Completion Date :||May 31, 2022|
Experimental: Treatment (docetaxel, ramucirumab, pembrolizumab)
Patients receive docetaxel IV over 60 minutes, ramucirumab IV over 60 minutes, and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- 6-month progression-free survival (PFS) rate [ Time Frame: up to 6 months ]Will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be reported and its 95% confidence intervals will be estimated using the Clopper-Pearson method. PFS rates of two patient groups stratified by binary biomarker (PD-L1 and KRAS status), respectively will be estimated with the Kaplan-Meier method and compared using the log-rank test, respectively. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of PD-L1 and KRAS status on the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.
- Incidence of adverse events [ Time Frame: Up to 30 days after the last dose of study treatment ]Will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Overall toxicity incidence as well as toxicity profiles will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. Proportion of acute and late toxicity will be reported, and 95% confidence intervals will be estimated using the Clopper-Pearson method.
- Overall response rate [ Time Frame: Through study completion, an average of 1 year ]Will be determined per RECIST 1.1 and immune-modified Response Evaluation Criteria in Solid Tumors.
- Overall survival (OS) [ Time Frame: up to 10 years ]OS and rates of two patient groups stratified by binary biomarker (PD-L1 and KRAS status), respectively will be estimated with the Kaplan-Meier method and compared using the log-rank test, respectively. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of PD-L1 and KRAS status on the patients' OS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04340882
|Contact: Erin T. Davis, MPH, CCRCfirstname.lastname@example.org|
|Contact: Mashunte Holmes, PhDemail@example.com|
|United States, Georgia|
|Winship Cancer Institute of Emory University||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Badi El Osta, MD 404-778-1900 firstname.lastname@example.org|
|Principal Investigator: Badi El Osta, MD|
|Principal Investigator:||Badi El Osta, MD||Emory University|