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Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors

ConditionsBladder AdenocarcinomaBladder Clear Cell AdenocarcinomaBladder Mixed AdenocarcinomaBladder Neuroendocrine CarcinomaBladder Small Cell Neuroendocrine CarcinomaBladder Squamous Cell CarcinomaChromophobe Renal Cell CarcinomaCollecting Duct CarcinomaInvasive Bladder Giant Cell Urothelial CarcinomaInvasive Bladder Lymphoepithelioma-Like CarcinomaInvasive Bladder Nested Urothelial CarcinomaInvasive Bladder Plasmacytoid Urothelial CarcinomaInvasive Bladder Sarcomatoid Urothelial CarcinomaInvasive Bladder Urothelial CarcinomaKidney Medullary CarcinomaLarge Cell Neuroendocrine CarcinomaMalignant Testicular Leydig Cell TumorMalignant Testicular Sertoli Cell TumorMetastatic Bladder CarcinomaMetastatic Bladder Clear Cell (Glycogen-Rich) Urothelial CarcinomaMetastatic Bladder Giant Cell Urothelial CarcinomaMetastatic Bladder Large Cell Neuroendocrine CarcinomaMetastatic Bladder Lipid-Rich Urothelial CarcinomaMetastatic Bladder Micropapillary Urothelial CarcinomaMetastatic Bladder Plasmacytoid Urothelial CarcinomaMetastatic Bladder Sarcomatoid Urothelial CarcinomaMetastatic Bladder Small Cell Neuroendocrine CarcinomaMetastatic Bladder Squamous Cell CarcinomaMetastatic Chromophobe Renal Cell CarcinomaMetastatic Kidney Medullary CarcinomaMetastatic Malignant Genitourinary System NeoplasmMetastatic Papillary Renal Cell CarcinomaMetastatic Penile CarcinomaMetastatic Prostate Small Cell Neuroendocrine CarcinomaMetastatic Sarcomatoid Renal Cell CarcinomaMetastatic Urethral CarcinomaPapillary Renal Cell CarcinomaSarcomatoid Renal Cell CarcinomaStage IV Bladder Cancer AJCC v8Stage IV Penile Cancer AJCC v8Stage IV Renal Cell Cancer AJCC v8Stage IV Urethral Cancer AJCC v8Stage IVB Prostate Cancer AJCC v8Urachal AdenocarcinomaUrethral Clear Cell Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1

One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.

Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded

Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma (Cohort B) - must be pure (per World Health Organization [WHO] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma

Disqualifiers

None

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood and urine sample collection

  • Bone Scan

    Procedure/Surgery

    Undergo bone scan

  • Cabozantinib S-malate

    Drug

    Given PO

  • Computed Tomography

    Procedure/Surgery

    Undergo CT and/or PET/CT scan

  • Echocardiography Test

    Procedure/Surgery

    Undergo echocardiography

  • Ipilimumab

    Biological/Vaccine

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Nivolumab

    Biological/Vaccine

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET/CT scan

Treatment groups

314 Participants
are divided into 1 treatment group
Group A: Treatment (cabozantinib, nivolumab, ipilimumab)Experimental treatment 9 interventions

Trial outcomes

Primary outcomes

1

Objective response rate (ORR)

An objective response is defined as a confirmed complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Will be estimated by the number of confirmed objective responses divided by the total number of evaluable patients. Confidence intervals for the true ORR will be calculated.

Time frame
Up to 5 years

Secondary outcomes

1

Duration of response

Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.

Time frame
From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
2

Progression-free survival (PFS)

The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.

Time frame
From start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years
3

Overall survival

The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.

Time frame
Up to 5 years
4

Clinical benefit rate (CBR)

A confirmed clinical benefit is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart or a confirmed stable disease at two consecutive tumor assessments at least 3 months apart. The CBR will be estimated by the number of patients with confirmed clinical benefit divided by the total number of evaluable patients. Confidence intervals for the true CBR will be calculated using exact binomial confidence intervals.

Time frame
Up to 5 years

Other outcomes

1

Effects of treatment in patients with bone-only disease

The bone-only tumor patients will be evaluated in an exploratory fashion (if no RECIST measurements are available). A maximum of 15 patients with bone-only disease will be enrolled and evaluated using PFS for a descriptive analysis of the effect of treatment.

Time frame
Up to 5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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