CYTO Reductive Surgery in Kidney Cancer Plus Immunotherapy and Targeted Kinase Inhibition

NCT04322955 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAS6927
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine if the use of immunotherapy nivolumab and the targeted therapy cabozantinib prior to removal of the kidney, will increase the number subjects who are without any visible kidney cancer in their body at some point during the course of treatment.

Conditions

Kidney Cancer; Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with a Complete Response

  The percentage of participants with a complete response following treatment. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

  Up to 5 years after completion of treatment

Secondary Outcomes (5)

• Median Size Reduction of the Primary Tumor

  12 weeks

• Progression Free Survival (PFS)

  Up to 5 years after completion of treatment

• Response Rate

  Up to 5 years after completion of treatment

• Overall Survival

  Up to 5 years after completion of treatment

• Surgical Outcomes

  Up to 5 years after completion of treatment

Study Arms (1)

Treatment with cabozantinib and nivolumab with nephrectomy

EXPERIMENTAL

All study participants will receive the same study medications, cabozantinib and nivolumab. The study drug, nivolumab, will be administered through an IV infusion every 4 weeks and cabozantinib will be administered orally daily. Initially participants will receive study treatment for 12 weeks. The cabozantinib will then be stopped prior to the nephrectomy. Initially patients enrolled on the study will be assigned to cohort 1. Patients who are assigned to cohort 1 will be treated with cabozantinib until 21 days prior to surgery. A patient in cohort 1 will be evaluable for assessment of the cabozantinib washout interval ("evaluable patients") if they 1. complete at least 10 of the 14 scheduled cabozantinib doses in the two week period prior to stopping cabozantinib AND 2. have surgical resection of the primary tumor. In cohort 2, subjects will receive cabozantinib until 14 days prior to nephrectomy.

Drug: Cabozantinib; Drug: Nivolumab; Procedure: Cytoreductive nephrectomy

Interventions

Cabozantinib DRUG

2 x 20 mg capsules taken orally daily

Also known as: XL184

Treatment with cabozantinib and nivolumab with nephrectomy

Nivolumab DRUG

480mg IV on first day of each 28-day cycle

Also known as: BMS-936558

Treatment with cabozantinib and nivolumab with nephrectomy

Cytoreductive nephrectomy PROCEDURE

Surgery removing as much tumor tissue as possible, possibly including surrounding tissues.

Treatment with cabozantinib and nivolumab with nephrectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information.
• Age ≥ 18years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 28 days prior to registration.
• Radiographically consistent with metastatic renal cell carcinoma (with subsequent pathologic confirmation of renal cell carcinoma with a clear cell component) OR histological/ cytological evidence of metastatic renal cell carcinoma with a clear cell component
• Measurable tumor in the kidney according to RECIST 1.1
• No prior therapy for metastatic renal cell carcinoma
• Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 14 days prior to registration.
• Females of childbearing potential must have a negative serum pregnancy test during screening, within 14 days of Cycle 1 Day 1. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

You may not qualify if:

• Patients who had previously undergone nephrectomy for renal cancer are excluded
• Uncontrolled bleeding, hypertension, or cardiovascular disease.
• Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4 inhibitors
• The subject has active brain metastases or epidural disease
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment.
• The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥1.3 x the laboratory upper limit of normal (ULN)
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, thrombin or Factor Xa inhibitors. Aspirin (up to 325 mg/day), low-dose warfarin (≤1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
• 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 within 3 months before the first dose of study treatment
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• 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
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment
• Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study start
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening

Sponsors & Collaborators

• Mark Stein: lead
• Exelixis: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (4)

The Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44012, United States

RECRUITING

Ohio State University Wexner Medical Center

Columbus, Ohio, 43221, United States

RECRUITING

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

cabozantinib; Nivolumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mark N Stein, MD

  Associate Professor of Medicine Division of Hematology/Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Nurse Navigator

CONTACT

212-342-5162; cancerclinicaltrials@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine Division of Hematology/Oncology

Model Details: Initially patients enrolled on the study will be assigned to Cohort 1. Patients assigned to Cohort 1 will have the cabozantinib held for three weeks prior to removal of the kidney. A patient in cohort 1 will be evaluable for assessment of the cabozantinib washout interval ("evaluable patients") if they 1. complete at least 10 of the 14 scheduled cabozantinib doses in the two week period prior to stopping cabozantinib AND 2. have surgical resection of the primary tumor. In cohort 2, subjects will receive cabozantinib until 14 days prior to nephrectomy.

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: March 26, 2020
• Study Start: June 22, 2020
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: April 25, 2025

Record last verified: 2025-04

Locations

US (4)