Ph3 of immunotherapy Based Drug Combo w/wo Cytoreductive Nephrectomy for metastatic RCC
Phase III Trial of Immunotherapy-Based Combination Therapy with or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)
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Clinical Trial Information
Trial Contact: Bobe Cortes, Estefania
Trial Phone: 321.841.6626
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IRB No: C23.044.02
Protocol Abbrev: S1931-PROBE
Principal Investigator: Hatem Hassanein, MD
Phase: Drug: Phase III
Age Group: Adult
Secondary Protocol No: S1931_PROBE
Treatment: Active Comparator: Arm 1: Continued Systemic Therapy Only Nivolumab 240 mg IV 1 q 2 weeks -OR- Nivolumab 480 mg IV 1 q 4 weeks -OR- Pembrolizumab 200 mg IV 1 q 3 weeks Axitinib 5 mg oral Daily BID -OR- Avelumab 10 mg/kg IV 1 q 2 weeks Axitinib 5 mg oral Daily BID Experimental: Arm 2: Nephrectomy and Continued Systemic Therapy Continued systemic therapy as above, plus: Radical or partial nephrectomy may be performed using laparoscopic, open, or robotic approaches. Surgery should be performed within 8 weeks of randomization.
Therapies Involved: Medication
ClinicalTrials.gov ID: NCT04510597
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Objective
To compare overall survival in participants with newly diagnosed metastatic renal cell carcinoma who are randomized to receive immune checkpoint inhibitor-based combination treatment plus cytoreductive nephrectomy versus immune checkpoint inhibitor-based combination treatment alone.
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Key Eligibility
Inclusion Criteria:
STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
STEP 1 REGISTRATION: Participants must have primary tumor in place
STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:
Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast
Scans must be performed within the following timeframes:
Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment
STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2
• STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
Stable disease
Partial response
The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1
STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
2 infusions of nivolumab + 1 infusion of ipilimumab
2 infusions of pembrolizumab
2 infusions of avelumab
STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
STEP 2 REGISTRATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
STEP 2 REGISTRATION: Serum creatinine =< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)
Exclusion Criteria:
STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:
Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:
Treatment naive participants must not have received any pre-randomization treatment.
Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:
4 infusions of nivolumab
4 infusions of ipilimumab
4 infusions of pembrolizumab
7 infusions of avelumab
STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:
Treatment naive participants must not have received any immunotherapy within a year of registration
Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
