Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, Pembrolizumab, Nivolumab and Atezolizumab in Treating Patients With Advanced Melanoma, Lung, or Kidney Cancer
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|ClinicalTrials.gov Identifier: NCT03050060|
Recruitment Status : Suspended (Under review)
First Posted : February 10, 2017
Last Update Posted : May 17, 2019
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Kidney Carcinoma Recurrent Melanoma Recurrent Lung Non-Small Cell Carcinoma Recurrent Renal Cell Carcinoma Stage IV Cutaneous Melanoma AJCC v6 and v7 Stage IV Non-Small Cell Lung Cancer AJCC v7 Stage IV Renal Cell Cancer AJCC v7||Drug: Atezolizumab Radiation: Hypofractionated Radiation Therapy Other: Laboratory Biomarker Analysis Drug: Nelfinavir Mesylate Biological: Nivolumab Biological: Pembrolizumab Drug: Nelfinavir||Phase 2|
I. Safety, tolerability and preliminary assessment of overall response rate (ORR) to combination of hypofractionated radiotherapy with PD1/PDL1 immune checkpoint and nelfinavir mesylate (nelfinavir).
I. Correlate overall response rate (ORR) with: smoking status, underlying genetic mutations if known (e.g.: Kras, BRAF) circulating cell-free deoxyribonucleic acid (cfDNA), circulating tumor cells, PDL-1 expression in tumor and peripheral blood T cell receptor repertoire by sequencing.
II. Progression-free survival (PFS)-6 (systemic control): the proportion of patients who are free from progression at 6 months.
III. Overall survival.
IV. The type and frequency of adverse events.
Beginning 7-14 days prior to start of pembrolizumab, nivolumab, or atezolizumab, patients receive nelfinavir mesylate orally (PO) twice daily (BID) on days 1-14 up to 11-12 weeks. Patients also receive pembrolizumab, nivolumab or atezolizumab intravenously (IV) over 30-60 minutes on day 1. Courses repeat every 14-21 days in the absence of disease progression or unacceptable toxicity. Patients then undergo hypofractionated radiation therapy over 3-14 days starting after course 1 and before course 3 of pembrolizumab, nivolumab or atezolizumab.
After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||ImmunoRad: Stratified Phase II Trial of Image Guided Hypofractionated Radiotherapy With Concurrent Nelfinavir and Immunotherapy in Advanced Melanoma, Lung Cancer, and Renal Cell Carcinoma|
|Actual Study Start Date :||June 9, 2017|
|Estimated Primary Completion Date :||December 1, 2021|
|Estimated Study Completion Date :||December 1, 2021|
Experimental: Treatment (nelfinavir, immunotherapy, radiation therapy)
Beginning 7-14 days prior to start of pembrolizumab, nivolumab, or atezolizumab, patients receive nelfinavir mesylate PO BID on days 1-14 up to 11-12 weeks. Patients also receive pembrolizumab, nivolumab or atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 14-21 days in the absence of disease progression or unacceptable toxicity. Patients then undergo hypofractionated radiation therapy over 3-14 days starting after course 1 and before course 3 of pembrolizumab, nivolumab or atezolizumab.
Radiation: Hypofractionated Radiation Therapy
Undergo hypofractionated radiation therapy
Other: Laboratory Biomarker Analysis
Drug: Nelfinavir Mesylate
- Response rate [ Time Frame: Up to 2 years ]Will be determined by immune-related Response Evaluation Criteria in Solid Tumor 1.1.
- Overall survival [ Time Frame: Up to 2 years ]
- Incidence of adverse events [ Time Frame: Up to 2 years ]Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
- Immune correlative studies including changes in T-cell repertoire [ Time Frame: Up to 2 years ]
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): NCT03050060
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Ramesh Rengan||Fred Hutch/University of Washington Cancer Consortium|