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Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, Pembrolizumab, Nivolumab and Atezolizumab in Treating Patients with Advanced Melanoma, Lung, or Kidney Cancer

Trial Status: Temporarily Closed to Accrual and Intervention

This phase II trial studies how well image guided hypofractionated radiation therapy works with nelfinavir mesylate, pembrolizumab, nivolumab, and atezolizumab in treating patients with melanoma, lung cancer, or kidney cancer that has spread. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Nelfinavir mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, nivolumab and atezolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving hypofractionated radiation therapy, nelfinavir mesylate, pembrolizumab, nivolumab and atezolizumab may work better in treating patients with melanoma, lung, or kidney cancer.

Inclusion Criteria

  • Disease eligibility and stage * Histologically confirmed diagnosis of melanoma, non-small cell lung cancer (NSCLC), or renal carcinoma * Previously treated or previously untreated stage IV melanoma, stage IV or recurrent lung cancer, and metastatic renal cancer by American Joint Committee on Cancer (AJCC) staging criteria * Presence of a lesion that is suitable for hypofractionated radiotherapy
  • Subjects must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria independent of the lesion to be irradiated. Prior checkpoint inhibitor immunotherapy or chemotherapy is allowed as long as the last dose was received > 14 days prior to enrollment
  • Eastern Cooperative Oncology Group (ECOG) 0-2
  • Acceptable marrow function and hematologic indices for PD1/PDL1 immune checkpoint inhibitor and nelfinavir as per standard of care
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Subjects who have had immunotherapy, chemotherapy, or radiation therapy within 14 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Subjects may not be receiving other investigational agents
  • Patients with untreated/active brain metastases as documented by computed tomography (CT) or magnetic resonance imaging (MRI) within 2 months of study enrollment
  • Allergy or intolerance to nelfinavir or selected PD1/PDL1 immune checkpoint inhibitor
  • Patients requiring steroids or other immunosuppressive therapy; low-dose or topical steroids are allowable if being used as replacement therapy
  • Patients receiving anti-retroviral therapy or other agents that are contra-indicated with nelfinavir due to drug-drug interactions
  • Pregnant or lactating patients
  • Prior radiation that precludes delivery of hypofractionated radiotherapy

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: TEMPORARILY_CLOSED_TO_ACCRUAL_AND_INTERVENTION
Contact: Ramesh Rengan
Phone: 206-598-4100
Email: rengan@uw.edu

PRIMARY OBJECTIVES:

I. To evaluate the response rate (complete [CR] or partial [PR] response, confirmed and unconfirmed) by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 in:

Ia. Patients with: non-small cell lung cancer, melanoma, or renal cell carcinoma that is either naive or refractory to anti-PD-L1 or PD-L1 therapy;

Ib. Who are treated with: Hypofractionated radiotherapy, anti-PD1/PD-L1 therapy and nelfinavir.

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of the regimen as determined by the rate of grade 4 hepatoxicity.

II. To evaluate the frequency and severity of toxicities by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 attributed to treatment.

III. To evaluate progression-free survival within each disease and prior treatment cohort.

IV. To evaluate overall survival within each disease and prior treatment cohort

V. To evaluate the association between response and 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 within each disease and prior treatment cohort.

OUTLINE:

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. Cycles 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 cycle 1 and before cycle 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.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Fred Hutch / University of Washington Cancer Consortium

Principal Investigator
Ramesh Rengan

  • Primary ID RG3117000
  • Secondary IDs NCI-2016-01816, 9712
  • Clinicaltrials.gov ID NCT03050060