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CYTO Reductive Surgery in Kidney Cancer Plus Immunotherapy and Targeted Kinase Inhibition (Cyto-KIK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04322955
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : April 4, 2022
Sponsor:
Collaborators:
Exelixis
Bristol-Myers Squibb
Information provided by (Responsible Party):
Mark Stein, Columbia University

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.

Condition or disease Intervention/treatment Phase
Kidney Cancer Renal Cell Carcinoma Drug: Cabozantinib Drug: Nivolumab Procedure: Cytoreductive nephrectomy Phase 2

Detailed Description:
People with metastatic kidney cancer are usually treated with medications to slow the growth of the cancer. In addition, people who still have the kidney where the cancer started may have the kidney removed during the course of treatment. This surgery is done in order to decrease the amount of tumor in the body. This surgery is referred to as a cytoreductive nephrectomy. In the current study, nivolumab, an immune checkpoint inhibitor, is being administered in combination with cabozantinib, a targeted therapy. The combination of nivolumab and cabozantinib is FDA approved for the treatment of metastatic kidney cancer. In this study, treatment consists of cabozantinib and nivolumab plus a cytoreductive nephrectomy. Eligible subjects, who have not received prior therapy for metastatic clear cell renal cell carcinoma, are treated with cabozantinib and nivolumab for approximately 3 months prior to undergoing cytoreductive nephrectomy. After nephrectomy, patients who are benefiting from treatment may resume cabozantinib and nivolumab. This study will help investigators to understand the immune effects of cabozantinib and nivoluamb in the kidney tumor and will provide information on the potential clinical benefit associated with cytoreductive nephrectomy in combination with cabozanitnib and nivolumab.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cyto-KIK; TRIAL (CYTO Reductive Surgery in Kidney Cancer Plus Immunotherapy (Nivolumab) and Targeted Kinase Inhibition (Cabozantinib)
Actual Study Start Date : June 22, 2020
Estimated Primary Completion Date : May 2026
Estimated Study Completion Date : February 2027


Arm Intervention/treatment
Experimental: Treatment with cabozantinib and nivolumab with nephrectomy

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
2 x 20 mg capsules taken orally daily
Other Name: XL184

Drug: Nivolumab
480mg IV on first day of each 28-day cycle
Other Name: BMS-936558

Procedure: Cytoreductive nephrectomy
Surgery removing as much tumor tissue as possible, possibly including surrounding tissues.




Primary Outcome Measures :
  1. Percentage of Participants with a Complete Response [ Time Frame: Up to 5 years after completion of treatment ]
    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.


Secondary Outcome Measures :
  1. Median Size Reduction of the Primary Tumor [ Time Frame: 12 weeks ]
    Median size reduction of the primary tumor after treatment for 12 weeks prior to nephrectomy will be determined using RECIST 1.1 criteria applied to the primary tumor.

  2. Progression Free Survival (PFS) [ Time Frame: Up to 5 years after completion of treatment ]
    PFS is defined as the time from the time of first treatment on study until disease's progression or death as a result of any cause.

  3. Response Rate [ Time Frame: Up to 5 years after completion of treatment ]
    Response rate will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST1.1.

  4. Overall Survival [ Time Frame: Up to 5 years after completion of treatment ]
    Overall survival will be measured from the time of first treatment on study until death or last follow-up.

  5. Surgical Outcomes [ Time Frame: Up to 5 years after completion of treatment ]
    Surgical outcomes will be assessed by the Clavien-Dindo classification system.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent and HIPAA authorization for release of personal health information.
  2. Age ≥ 18years at the time of consent.
  3. ECOG Performance Status of 0-1 within 28 days prior to registration.
  4. 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
  5. Measurable tumor in the kidney according to RECIST 1.1
  6. No prior therapy for metastatic renal cell carcinoma
  7. Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 14 days prior to registration.
  8. 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
  9. 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.
  10. 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

Exclusion Criteria:

  1. Patients who had previously undergone nephrectomy for renal cancer are excluded
  2. Uncontrolled bleeding, hypertension, or cardiovascular disease.
  3. Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4 inhibitors
  4. The subject has active brain metastases or epidural disease
  5. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment.
  6. The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥1.3 x the laboratory ULN
  7. 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
  8. Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
  9. Hemoptysis of ≥0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment
  10. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  11. 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
  12. Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment
  13. 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
  14. Cardiovascular disorders including:

    • 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 BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 14 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 registration.
  15. Severe active infection requiring systemic treatment within 28 days before the first dose of study treatment
  16. Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
  17. Major surgery (e.g., 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 (e.g., simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  18. History of organ transplant
  19. Concurrent uncompensated hypothyroidism
  20. Unable to swallow tablets
  21. Active infection requiring systemic therapy
  22. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  23. Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least 2 years.
  24. Active central nervous system (CNS) metastases
  25. Treatment with any investigational drug within 28 days prior to registration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04322955


Contacts
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Contact: Research Nurse Navigator 212-342-5162 cancerclinicaltrials@cumc.columbia.edu

Locations
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United States, New Jersey
The Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Eric Singer    732-235-3272    eric.singer@rutgers.edu   
United States, New York
Columbia University Irving Medical Center Recruiting
New York, New York, United States, 10032
Contact: Research Nurse Navigator    212-342-5162    cancerclinicaltrials@cumc.columbia.edu   
Principal Investigator: Mark N Stein, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44012
Contact: Moshe Ornstein, MD,MA    917-587-3359    ornstem@ccf.org   
Sponsors and Collaborators
Mark Stein
Exelixis
Bristol-Myers Squibb
Investigators
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Principal Investigator: Mark N Stein, MD Associate Professor of Medicine Division of Hematology/Oncology
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Responsible Party: Mark Stein, Associate Professor of Medicine Division of Hematology/Oncology, Columbia University
ClinicalTrials.gov Identifier: NCT04322955    
Other Study ID Numbers: AAAS6927
First Posted: March 26, 2020    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action