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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03050060
Recruitment Status : Suspended (Under review)
First Posted : February 10, 2017
Last Update Posted : February 25, 2020
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. 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.

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 Advanced Lung Non-Small Cell Carcinoma Advanced Melanoma Recurrent Lung Carcinoma Stage III Cutaneous Melanoma AJCC v7 Stage III Renal Cell Cancer AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Lung Non-Small 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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: N/A
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. 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.
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

Drug: Nelfinavir
Given PO




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


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From start of study treatment to death due to any cause, assessed up to 2 years ]
  2. Progression-free survival [ Time Frame: From start of treatment to progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, symptomatic deterioration, or death due to any cause, assessed up to 2 years ]
  3. Incidence of adverse events [ Time Frame: Up to 2 years ]
    Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  4. Immune correlative studies including changes in T-cell repertoire [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 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

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
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ramesh Rengan Fred Hutch/University of Washington Cancer Consortium
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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT03050060    
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 )
RG3117000 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: February 25, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Washington:
Kidney
Lung
Melanoma, Skin
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Carcinoma, Renal Cell
Skin Neoplasms
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Skin Diseases
Nelfinavir
Pembrolizumab