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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

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ClinicalTrials.gov Identifier: NCT03050060
Recruitment Status : Recruiting
First Posted : February 10, 2017
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Brief Summary:
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. Monoclonal antibodies, such as pembrolizumab, nivolumab and atezolizumab, 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.

Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Cancer Recurrent Melanoma Recurrent Non-Small Cell Lung 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 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

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. 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)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Drug: Atezolizumab
Given IV
Other Names:
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL3280A
  • MPDL328OA
  • RG7446
  • RO5541267
  • Tecentriq

Radiation: Hypofractionated Radiation Therapy
Undergo hypofractionated radiation therapy
Other Names:
  • Hypofractionated Radiotherapy
  • hypofractionation

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Nelfinavir Mesylate
Given PO
Other Names:
  • AG1343
  • Viracept

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. Response rate determined by immune-related Response Evaluation Criteria in Solid Tumor 1.1 [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  1. Immune correlative studies including changes in T-cell repertoire [ Time Frame: Up to 2 years ]
  2. Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ]
  3. Overall survival [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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 irradiated
  • Prior immunotherapy or chemotherapy is allowed as long as > 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 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

Information from the National Library of Medicine

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


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ramesh Rengan    206-598-4100    rengan@uw.edu   
Principal Investigator: Ramesh Rengan         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ramesh Rengan Fred Hutch/University of Washington Cancer Consortium

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT03050060     History of Changes
Other Study ID Numbers: 9712
NCI-2016-01816 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9712 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: February 14, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Carcinoma
Melanoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Pembrolizumab
Nivolumab
Atezolizumab
Antibodies, Monoclonal