Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Carcinoma, Medullary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Thyroid Cancer, Medullary

Renal Medullary Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anticoagulants

Anti-Infective Agents

Other Dietary Supplements

Amino Acids

Gemcitabine

Doxorubicin

Liposomal doxorubicin

Daunorubicin

Citric Acid

Sodium Citrate

Ixazomib

Glycine

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

HIV Protease Inhibitors

Protease Inhibitors

Neurotransmitter Agents

Citrate

INDUCTION: Patients receive ixazomib PO, gemcitabine IV over 90 minutes, and doxorubicin IV over 15-30 minutes on day 1. Treatment repeats every 14 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive ixazomib PO and gemcitabine IV over 90 minutes. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Doxorubicin Hydrochloride

Gemcitabine Hydrochloride

Ixazomib Citrate

Pavlos Msaouel

This phase II trial studies how well ixazomib, gemcitabine, and doxorubicin work in treating patients with kidney cancer that has spread to other places in the body (locally advanced or metastatic). Ixazomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ixazomib, gemcitabine, and doxorubicin may work better in treating patients with kidney cancer.

PRIMARY OBJECTIVE:

I. To determine the objective response rate (ORR) and disease control rate (DCR) of patients with locally advanced or metastatic renal medullary carcinoma (RMC) treated with combination of ixazomib with gemcitabine and doxorubicin.

SECONDARY OBJECTIVE:

I. To determine the overall survival (OS), progression-free survival (PFS), duration of response (DOR) and safety of the combination of ixazomib with gemcitabine and doxorubicin in patients with RMC.

EXPLORATORY OBJECTIVES:

I. To evaluate potential biomarkers, such as tumor tissue protein disulfide isomerase (PDI), binding immunoglobulin protein (BiP), and phosphorylated eIF2a (eIF2aP), as well as serum levels of interleukin 6 (IL-6), for patient stratification, and as pharmacodynamics measures of treatment response.

II. To determine, via the molecular profiling of biopsy and blood speciments, the mechanisms of resistance to the trial therapy (ixazomib + gemcitabine + doxorubicin).

OUTLINE:

INDUCTION: Patients receive ixazomib orally (PO), gemcitabine intravenously (IV) over 90 minutes, and doxorubicin IV over 15-30 minutes on day 1. Treatment repeats every 14 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive ixazomib PO and gemcitabine IV over 90 minutes. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 90 days, then every 3 months thereafter.

Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

Phase II Trial of Ixazomib Combined With Gemcitabine and Doxorubicin in Patients With Renal Medullary Carcinoma

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Gland and Hormone Related Diseases

Carcinoma, Squamous Cell

Prostatic Neoplasms

Urinary Bladder Neoplasms

Carcinoma, Ductal

Carcinoma, Transitional Cell

Adenocarcinoma, Clear Cell

Carcinoma, Small Cell

Leydig Cell Tumor

Sertoli Cell Tumor

Urethral Neoplasms

Penile Neoplasms

Thyroid Neoplasms

Thyroid Diseases

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Neoplasms, Squamous Cell

Urinary Bladder Diseases

Urethral Diseases

Penile Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Endocrine System Diseases

Sertoli-Leydig Cell Tumor

Sex Cord-Gonadal Stromal Tumors

Testicular Neoplasms

Testicular Diseases

Gonadal Disorders

Transitional Cell Carcinoma

Penile Cancer

Papillary Renal Cell Carcinoma

Chromophil Renal Cell Carcinoma

Chromophobe Renal Cell Carcinoma

Collecting Duct Carcinoma

Urethral Cancer

Urachal Adenocarcinoma

Sertoli-leydig Cell Tumors

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Nivolumab

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive cabozantinib PO, nivolumab IV and ipilimumab IV while on study. Patients undergo CT scan, MRI, PET and bone scans throughout the study.

Bone Scan

Cabozantinib S-malate

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Site Public Contact

Arnab Basu

Lance C. Pagliaro

Uzair B. Chaudhary

Anishka D'Souza

Nancy A. Dawson

Tareq Al Baghdadi

Hatem Hassanein

Mehmet A. Bilen

John M. Schallenkamp

Jeffrey A. Sosman

Thomas C. Westbrook

Walter M. Stadler

Vamsi K. Vasireddy

Bryan A. Faller

Ami Badami

Andrea B Apolo

This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that 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.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of cabozantinib s-malate (cabozantinib) combined with nivolumab and ipilimumab in the first or second-line (and beyond) setting for patients within each of the rare genitourinary (GU) variant histology group of interest, as measured by objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

II. To estimate the overall survival (OS) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

III. To estimate the clinical benefit rate (defined as complete response \[CR\] or partial response \[PR\] or stable disease \[SD\]) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

IV. To assess the safety of treating patients with rare variant histologies with cabozantinib combined with nivolumab and ipilimumab.

V. To support tissue banking and collection of clinical follow-up data for GU tract rare histological variants.

EXPLORATORY OBJECTIVES:

I. To assess effects of treatment in patients with bone-only disease by bone scan.

OUTLINE:

Patients receive cabozantinib orally (PO), nivolumab intravenously (IV) and ipilimumab IV while on study. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), positron emission tomography (PET) and bone scans throughout the study.

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

A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

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.

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.

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.

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

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.

Will be assessed using Common Terminology Criteria for Adverse Events version 5.0. The maximum of a particular AE will be determined for each patient. Tables will summarize the number and relative frequency of patients observing an AE as well as the number and relative frequency of patients experiencing any AE of grade 3 or greater.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer	NCT03587662	Metastatic Kidn... Metastatic Rena... SMARCB1 Negativ... Stage III Renal... Stage IV Renal ...	Doxorubicin Doxorubicin Hyd... Gemcitabine Gemcitabine Hyd... Ixazomib Ixazomib Citrat...	12 Years -	M.D. Anderson Cancer Center
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors	NCT03866382	Bladder Adenoca... Bladder Clear C... Bladder Mixed A... Bladder Neuroen... Bladder Small C... Bladder Squamou... Chromophobe Ren... Collecting Duct... Invasive Bladde... Invasive Bladde... Invasive Bladde... Invasive Bladde... Invasive Bladde... Invasive Bladde... Kidney Medullar... Large Cell Neur... Malignant Testi... Malignant Testi... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Chro... Metastatic Kidn... Metastatic Mali... Metastatic Papi... Metastatic Peni... Metastatic Pros... Metastatic Sarc... Metastatic Uret... Papillary Renal... Sarcomatoid Ren... Stage IV Bladde... Stage IV Penile... Stage IV Renal ... Stage IV Urethr... Stage IVB Prost... Urachal Adenoca... Urethral Clear ...	Bone Scan Cabozantinib S-... Computed Tomogr... Ipilimumab Magnetic Resona... Nivolumab Positron Emissi...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for metastatic kidney medullary carcinoma