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

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-09

Study Completion Date

2020-07-12

Brief Summary

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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.

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Detailed Description

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OUTLINE:

Beginning 7-14 days prior to start of pembrolizumab, nivolumab, or atezolizumab, patients receive nelfinavir mesylate orally (PO) twice daily (BID) on days 1-7 or 1-14 (dependent upon when treatment is started) up to 11-12 weeks. Patients also receive pembrolizumab, nivolumab or atezolizumab intravenously (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.

After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 2 years.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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 1-7 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.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

Given IV

Hypofractionated Radiation Therapy

Intervention Type RADIATION

Undergo hypofractionated radiation therapy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Nelfinavir Mesylate

Intervention Type DRUG

Given PO

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Atezolizumab

Given IV

Intervention Type DRUG

Hypofractionated Radiation Therapy

Undergo hypofractionated radiation therapy

Intervention Type RADIATION

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Nelfinavir Mesylate

Given PO

Intervention Type DRUG

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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MPDL 3280A MPDL 328OA MPDL-3280A MPDL3280A MPDL328OA RG7446 RO5541267 Tecentriq Hypofractionated Radiotherapy hypofractionation Radiation, Hypofractionated AG1343 Viracept BMS-936558 MDX-1106 NIVO ONO-4538 Opdivo Keytruda Lambrolizumab MK-3475 SCH 900475

Eligibility Criteria

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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; 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
* Miscellaneous: seville oranges, grapefruit, or grapefruit juice and/or pomelos, star fruit, exotic citrus fruits, or grapefruit hybrids.

Strong Inducers of CYP3A4:

* Glucocorticoids: cortisone (\> 50 mg), hydrocortisone (\> 40 mg), prednisone (\> 10 mg), methylprednisolone (\> 8 mg), dexamethasone (\> 1.5 mg)
* Anticonvulsants: phenytoin, carbamazepine, primidone, phenobarbital and other enzyme inducing anti-convulsant drugs (EIACD)
* Antibiotics: rifampin (rifampicin), rifabutin, rifapentine
* Miscellaneous: St. John's Wort, modafinil

Strong Inhibitors of CYP2C9:

• Antifungals: fluconazole; lists including medications and substances known or with the potential to interact with the CYP3A or 2C19

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No