Clinical Trials /

A Study of Nivolumab In Combination With Cabozantinib in Patients With Non-Clear Cell Renal Cell Carcinoma

NCT03635892

Description:

The purpose of this study is to compare any good and bad effects of using a combination of nivolumab (Opdivo®) and cabozantinib (Cabometyx®) in people with metastatic kidney cancer.

Related Conditions:
  • Non-Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Nivolumab In Combination With Cabozantinib in Patients With Non-Clear Cell Renal Cell Carcinoma
  • Official Title: A Phase 2 Open-Label Study of Nivolumab Combined With Cabozantinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma (CA209-9KU)

Clinical Trial IDs

  • ORG STUDY ID: 18-254
  • NCT ID: NCT03635892

Conditions

  • Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma
  • Unclassified Renal Cell Carcinoma
  • Papillary Renal Cell Carcinoma
  • Fumarate Hydratase Deficient Renal Cell Carcinoma
  • Succinate Dehydrogenase Deficient Renal Cell Carcinoma
  • Collecting Duct Renal Cell Carcinoma
  • Chromophobe Renal Cell Carcinoma

Interventions

DrugSynonymsArms
cabozantinibCABOMETYX®cabozantinib in combination with nivolumab
nivolumabOpdivocabozantinib in combination with nivolumab

Purpose

The purpose of this study is to compare any good and bad effects of using a combination of nivolumab (Opdivo®) and cabozantinib (Cabometyx®) in people with metastatic kidney cancer.

Trial Arms

NameTypeDescriptionInterventions
cabozantinib in combination with nivolumabExperimentalCycle length will be defined as 28 days. Treatment will include cabozantinib 40mg, self administered orally once daily on a continuous schedule (days 1-28), and nivolumab 240mg, administered intravenously on days 1 and 15 of each cycle ± 3 days. Patients will also apply Clobetasol topically to their hands and feet twice a day for the first 12 weeks of therapy. Treatment will be continued until confirmed disease progression, major toxicity, or withdrawal from the study for any reason. Continuation of Clobetasol beyond 12 weeks at investigator discretion as per standard management of Hand Foot Syndrome.
  • cabozantinib
  • nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Signed and dated IRB-approved Informed Consent Form

          -  Pathologic or histologically confirmed unresectable advanced or metastatic nccRCC

          -  0 or 1 prior systemic therapies, including treatment in the adjuvant setting

          -  Availability of a representative formalin fixed, paraffin embedded tumor specimen or
             fresh frozen tissue specimen that enables the definitive diagnosis of RCC, accompanied
             by an associated pathology report. Specimens can be collected by surgical resection or
             biopsy of the primary tumor or biopsy or resection of a metastatic lesion.

          -  Measurable disease, as defined by RECIST 1.1

          -  Age ≥18 years

          -  KPS ≥ 70

          -  Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior
             treatments, unless adverse events (AE(s)) are clinically nonsignificant and/or stable
             on supportive therapy.

          -  Adequate hematologic and end organ function, defined by the following laboratory
             results obtained within 14 days prior to the first study treatment:

               -  ANC ≥ 1500 cells/μL (without granulocyte colony stimulating factor support within
                  2 weeks prior to Cycle 1, Day 1)

               -  WBC counts ≥ 2500/μL and ≤ 15,000/μL without G-CSF

               -  Lymphocyte count ≥ 500/μL

               -  Platelet count ≥100,000/μL (without transfusion within 2 weeks prior to Cycle 1,
                  Day 1)

               -  Hemoglobin ≥9.0 g/dL (without transfusion within 2 weeks prior to Cycle 1, Day 1)

          -  Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline
             phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN if patient has
             documented bone metastases.

          -  Serum bilirubin ≤ 1.5 x ULN . Patients with known Gilbert disease who have serum
             bilirubin level ≤ 3 x ULN may be enrolled.

          -  Serum albumin ≥ 2.8 g/dl

          -  Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be
             enrolled.

          -  INR and aPTT ≤ 1.3 x ULN • within 14 days of first dose of study treatment.This
             applies only to patients who are not receiving therapeutic anticoagulation; patients
             receiving therapeutic anticoagulation should be on a stable dose.

          -  Creatinine ≤ 2.0 x ULN or Calculated Creatinine clearance ≥ 30mL/min

          -  For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile
             (absence of ovaries and/or uterus): agreement to use two adequate methods of
             contraception, including at least one method with a failure rate of ≥ 1% per year

          -  Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol)

          -  Sexually active fertile subjects and their partners must agree to use medically
             accepted methods of contraception (eg, barrier methods, including male condom, female
             condom, or diaphragm with spermicidal gel) during the course of the study and for 5
             months after the last dose of study treatment for females and 7 months for males.

          -  Female subjects of childbearing potential must not be pregnant at screening. Females
             of childbearing potential are defined as premenopausal females capable of becoming
             pregnant (ie, females who have had any evidence of menses in the past 12 months, with
             the exception of those who are surgically sterile as described above).

        However, women who have been amenorrheic for 12 or more months are still considered to be
        of childbearing potential if the amenorrhea is possibly due to prior chemotherapy,
        antiestrogens, low body weight, ovarian suppression or other reasons.

          -  Capable of understanding and complying with the protocol requirements and must have
             signed the informed consent document.

        Exclusion Criteria:

          -  Prior treatment with an immunotherapy agent including high dose IL-2, anti-CTLA-4,
             anti-PD1, and anti-PD-L1 agents

          -  Prior treatment with cabozantinib for non-clear cell RCC

          -  Receipt of any type of small molecule kinase inhibitor within 2 weeks of treatment.

          -  Receipt of any type of anti-cancer antibody, cytotoxic anticancer therapy, or any
             other investigational agents within 4 weeks of treatment start

          -  Known malignancies of the brain or spinal cord or leptomeningeal disease

          -  Patients requiring pain medication must be on a stable regimen at study entry

          -  Any condition requiring systemic treatment with corticosteroids (> 10 mg daily
             prednisone equivalents) or other immunosuppressive medications within 14 days prior to
             first dose of study drug. Inhaled steroids and adrenal replacement steroids > 10 mg
             daily prednisone equivalents are allowed in the absence of autoimmune disease

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently)

          -  Uncontrolled hypercalcemia (≥ 1.5 mmol/L ionized calcium or Ca ≥ 12 mg/dL or corrected
             serum calcium ≥ ULN) or symptomatic hypercalcemia requiring continued use of
             bisphosphonate therapy or denosumab

          -  Diagnosis of another malignancy within 2 years before first dose of study treatment,
             except for superficial skin cancers, or localized, low grade tumors deemed cured and
             not treated with systemic therapy

          -  Pregnant and lactating women History of severe allergic, anaphylactic, or other
             hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

          -  History of HIV infection

          -  Patients with active or chronic hepatitis B or hepatitis C infection

          -  Significant cardiovascular disease, such as New York Heart Association cardiac disease
             (Class II or greater), myocardial infarction within the previous 6 months, unstable
             arrhythmias, unstable angina, or EF < 50%

          -  Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg
             systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment

          -  Patients with known coronary artery disease, congestive heart failure not meeting the
             above criteria must be on a stable medical regimen that is optimized in the opinion of
             the treating physician, in consultation with a cardiologist if appropriate

          -  Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks
             before first dose of study treatment. Complete wound healing from major surgery must
             have occurred 1 month before first dose and from minor surgery (eg, simple excision,
             biopsy, tooth extraction) at least 10 days before first dose. Subjects with clinically
             relevant ongoing complications from prior surgery are not eligible

          -  History of stroke or transient ischemic attack within 6 months prior to Cycle 1, Day 1

          -  Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine
             parenteral hydration, parenteral nutrition, or tube feeding

          -  Evidence of abdominal free air not explained by paracentesis or recent surgical
             procedure

          -  Patients with a history of abdominal fistula, gastrointestinal perforation, or
             intraabdominal abscess within 6 months prior to study enrollment

          -  Other clinically significant disorders that would preclude safe study participation

               -  Serious non-healing wound/ulcer/bone fracture

               -  Uncompensated/symptomatic hypothyroidism

               -  Moderate to severe hepatic impairment (Child-Pugh B or C)

          -  Corrected QT interval calculated by the Frederica formula (QTcF) > 500 ms per
             elFectrocardiogram (ECG) within 28 days before first dose of study treatment Note: If
             a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at
             intervals of approximately 3 min must be performed within 30 min after the initial
             ECG, and the average of these three consecutive results for QTcF will be used to
             determine eligibility

          -  Inability to swallow tablets or capsules

          -  Previously identified allergy or hypersensitivity to components of the study treatment
             formulations

          -  Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable or will not be able to complete the entire study

          -  Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin
             and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel).

        Allowed anticoagulants are the following:

          -  Low-dose aspirin for cardio protection (per local applicable guidelines) is permitted

          -  Low-dose low molecular weight heparins (LMWH) are permitted

          -  Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known
             brain metastases who are on a stable dose of LMWH for at least 3 weeks before first
             dose of study treatment, and who have had no clinically significant hemorrhagic
             complications from the anticoagulation regimen or the tumor

               -  Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon
                  (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary
                  hemorrhage) within 12 weeks before first dose

               -  Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease
                  manifestation

               -  The subject has tumor invading or encasing any major blood vessels

               -  The subject has 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 cabozantinib

               -  Uncontrolled hypertension (>150 mmHg systolic or > 100 mmHg diastolic despite
                  optimal antihypertensive treatment)

               -  Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy
                  within 4 weeks before first dose of study treatment. Systemic treatment with
                  radionuclides within 6 weeks before the first dose of study treatment. Subjects
                  with clinically relevant ongoing complications from prior radiation therapy are
                  not eligible. Radiation for palliation is allowable on study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:objective response rate
Time Frame:2 years
Safety Issue:
Description:per RECIST v1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Nivolumab
  • Cabozantinib
  • 18-254

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