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

NCT03050060 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: 9712NCI-2016-01816P30CA015704RG3117000
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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 (advanced). 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.

Conditions

Metastatic Kidney Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Lung Non-Small Cell Cancer AJCC v7

Keywords

Kidney; Lung; Melanoma, Skin

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Will be determined by immune-related Response Evaluation Criteria in Solid Tumor 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT Scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.",

  Up to 6 months after initiating treatment

Secondary Outcomes (4)

• Overall Survival

  From start of study treatment to death due to any cause, assessed up to 2 years

• Progression-free Survival

  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

• Number of Adverse Events

  Adverse events were assessed up to 6 months from start of study treatment and All Cause Mortality was assessed upto 2 years from start of study treatment.

• Immune Correlative Studies: Changes in T-cell Repertoire

  Up to 6 months

Study Arms (1)

Treatment (nelfinavir, immunotherapy, radiation therapy)

EXPERIMENTAL

Beginning 7-14 days prior to start of pembrolizumab, nivolumab, or atezolizumab, patients receive nelfinavir mesylate PO BID on days 1-7 or 1-14 (dependent upon when treatment is started) up to 11-12 weeks. Patients also receive pembrolizumab, nivolumab or atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21-28 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. The study will exclude irradiation of liver metastases as an added precaution.

Drug: Atezolizumab; Radiation: Hypofractionated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Nelfinavir Mesylate; Biological: Nivolumab; Biological: Pembrolizumab

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (nelfinavir, immunotherapy, radiation therapy)

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated radiation therapy

Also known as: Hypofractionated Radiotherapy, hypofractionation, Radiation, Hypofractionated

Treatment (nelfinavir, immunotherapy, radiation therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nelfinavir, immunotherapy, radiation therapy)

Nelfinavir Mesylate DRUG

Given PO

Also known as: AG1343, Viracept

Treatment (nelfinavir, immunotherapy, radiation therapy)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nelfinavir, immunotherapy, radiation therapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (nelfinavir, immunotherapy, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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; by active brain metastases - we mean - actively symptomatic brain metastases requiring steroids
• 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
• Strong Inhibitors of CYP3A4:
• Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin
• HIV: non-nucleoside reverse transcriptase inhibitors (delavirdine, nevirapine), protease inhibitors (ritonavir, indinavir, lopinavir/ritonavir, saquinavir), cobicistat-boosted antiretrovirals (e.g., elvitegravir); NOTE: Clinical trials have demonstrated that there are no clinically significant drug-drug interactions between nelfinavir and the following antiretrovirals: efavirenz (strong CYP3A4 inhibitor), etravirine (strong CYP3A4 inhibitor); therefore, these antiretrovirals will not be excluded. • Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole, posaconazole
• Antidepressants: nefazodone
• Antidiuretic: conivaptan
• GI: cimetidine, aprepitant
• Hepatitis C: boceprevir, telaprevir

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Melanoma

Interventions

atezolizumab; Radiation Dose Hypofractionation; Radiation; Nelfinavir; Nivolumab; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Physical Phenomena; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Ramesh Rengan, Department Chair
• Organization: University of Washington

rengan@uw.edu

206-598-4100

Study Officials

• Ramesh Rengan

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 10, 2017
• Study Start: June 9, 2017
• Primary Completion: October 1, 2018
• Study Completion: July 12, 2020
• Last Updated: June 22, 2022
• Results First Posted: June 22, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)