Trial studying safety and effects for Bladder Adenocarcinoma
Official title Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
ClinicalTrials.gov ID: NCT03866382
What this study is testing
What is Cabozantinib S-malate?
An investigational oral medicine being studied for treating rare bladder adenocarcinoma that has spread to other parts of the body. It is designed to block enzymes that help tumor cells grow.
Also referred to as Cabometyx, Cometriq.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This study is testing whether adding cabozantinib to the immune drugs nivolumab and ipilimumab improves treatment for rare cancers that have spread to other parts of the body.
- Who it's for
- You may be able to join if you have a rare cancer that has spread and have no other treatment options.
- What's involved
- You would receive the three drugs together. You will have regular visits to check how you are doing and to monitor side effects.
- Time commitment
- The study lasts until the treatment stops or you leave, with visits every few weeks to monitor progress.
- Phase 2: a mid-size study of how well it works
- Time commitment: about 5 years
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- 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...
- Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma (Cohort B) - must be pure (per World Health...
- Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e.
See the full eligibility criteria
Who can join
- 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.
- 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.
- Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
- Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly \> or equal \~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid...
- Any penile cancer (Cohort E)
- Sarcomatoid renal cell carcinoma (Cohort F) - Tumor should be predominantly sarcomatoid \~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade...
- Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to (Cohort G) : Micropapillary (Tumor should show predominantly \> or equal 50% micropapillary architecture), giant cell...
- Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial
- Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly \~ 50% sarcomatoid differentiation
- Renal medullary carcinoma (Cohort I) - Per World Health Organization (WHO) definition, ideally confirmed with immunostains
- Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
- Renal Collecting Duct Carcinoma (Cohort K) - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of...
- Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
- H\&E slides from diagnostic tumor tissue for retrospective central pathology review
- Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or...
- Age \>= 18 years
- Patients must be able to swallow oral formulation of the tablets
- Karnofsky performance status \>= 80%
- Absolute neutrophil count (ANC) \>= 1,000/mcL
- Platelet count \>= 75,000/mcL
- Total bilirubin =\< 1.5 x upper limit of normal (ULN). For people with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =\< 3.0 mg/dL
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal (ULN) (or =\< 5 x ULN for patients with liver metastases or Gilbert's disease)
- Creatinine =\ = 40 mL/min/1.73 m\^2 (calculated using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
- Hemoglobin \>= 9 g/dL (transfusion of packed red blood cells [PRBCs] allowed)
- Serum albumin \>= 3.2 g/dL
- Lipase and amylase =\< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis
- Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed.
- No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
- Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current...
- Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies...
- Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g.
- Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible
- Women of childbearing potential must have a negative pregnancy test =\< 7 days prior to registration
- Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not...
- Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have potential for teratogenic or abortifacient effects.
- The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment
- To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
- To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment
- To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
- To any other site(s) within 2 weeks before the first dose of study treatment
- The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
- The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
- The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment.
- The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment
- The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant...
- The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid...
- No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=\< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
- No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors
- Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information.
- Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
- Hemoptysis of \>= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment
- Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
- The patient has no tumor invading any major blood vessels
- The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of...
- Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
- Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic, or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
- The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 28 days before randomization.
- Any history of congenital long QT syndrome
- Unstable angina pectoris
- Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)
- Stroke (including transient ischemic attack [TIA], or other ischemic event)
- Myocardial infarction
- Cardiomyopathy
- Active peptic ulcer disease
- Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome
- Abdominal fistula or genitourinary fistula
- Gastrointestinal perforation
- Bowel obstruction or gastric outlet obstruction
- Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of...
- Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible
- Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment
- Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
- History of organ or allogeneic stem cell transplant
- Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone [TSH], thyroid replacement...
- Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has...
- Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies...
- Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery
- No history of severe hypersensitivity reaction to any monoclonal antibody
- No evidence of active malignancy, requiring systemic treatment within 2 years of registration
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study
- No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
- No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids.
The study team makes the final eligibility decision.
Where it is enrolling
- Birmingham, Alabama, United States
- Phoenix, Arizona, United States
- Scottsdale, Arizona, United States
- Los Angeles, California, United States
- Newport Beach, California, United States
- Washington D.C., District of Columbia, United States
- Fort Lauderdale, Florida, United States
- Orlando, Florida, United States
- Atlanta, Georgia, United States
- Boise, Idaho, United States
- Caldwell, Idaho, United States
- Coeur d'Alene, Idaho, United States
- Nampa, Idaho, United States
- Post Falls, Idaho, United States
- Sandpoint, Idaho, United States
- Chicago, Illinois, United States
- Danville, Illinois, United States
- Decatur, Illinois, United States
- Effingham, Illinois, United States
- Mattoon, Illinois, United States
+ 153 more site(s).
Compensation & support
A stipend or payment for your time may be offered.
No amount is published here because ClinicalTrials.gov has no reliable field for payment or travel support. Ask the study team what's actually covered (payment for your time, travel, parking, or other study costs), and never join a trial for the compensation alone.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team, so confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The study runs about 5 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Birmingham, Alabama, United States; Phoenix, Arizona, United States; Scottsdale, Arizona, United States; Los Angeles, California, United States; Newport Beach, California, United States; Washington D.C., District of Columbia, United States and 167 more locations. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.