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

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ClinicalTrials.gov Identifier: NCT04322955
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : March 26, 2020
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 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 is being administered in combination with cabozantinib. Both of these drugs are FDA approved medications for the treatment of metastatic kidney cancer. Previous studies have demonstrated that these two medications can be combined together without significantly increasing the side effects beyond what is expected from each medicine individually. The combination of nivolumab and cabozantinib for the treatment of metastatic kidney cancer is an investigational regimen and not FDA approved for the treatment of kidney cancer.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Sequential Assignment
Intervention Model Description: The first three to six subjects (group 1) will have the cabozantinib held for three weeks prior to removal of the kidney. If there are no unexpected side effects from the surgery, then future subjects (group 2) will have the cabozantinib stopped for two weeks prior to the 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)
Estimated Study Start Date : March 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. The first three to six subjects (group 1) will have the cabozantinib held for three weeks prior to removal of the kidney. If there are no unexpected side effects from the surgery, then future subjects (group 2) will have the cabozantinib stopped for two weeks prior to the 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.



Information from the National Library of Medicine

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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:

  • 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.
  • Histological or 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:

    • White blood cell (WBC) ≥ 3,000/mm3
    • Absolute Neutrophil Count (ANC) ≥ 1,200/mm3
    • Hemoglobin (Hgb) ≥ 9 g/dL
    • Platelet ≥ 100,000
    • Calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula
    • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) ≤ 3 × ULN
    • Alanine aminotransferase (ALT) ≤ 3 × ULN
    • Albumin ≥ 2.8 g/dL
    • International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) within normal limits. Patients using low molecular weight heparin are allowed on study
  • Females of childbearing potential must have a negative serum pregnancy test during screening and within 24 hours of start of study drugs. 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

Exclusion Criteria:

  • 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 ≥1.3x the laboratory ULN within 7 days before the first dose of study treatment
  • 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
    • Concurrent uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 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.
    • Severe active infection requiring systemic treatment within 28 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
  • 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.
  • History of organ transplant
  • Concurrent uncompensated hypothyroidism
  • Unable to swallow tablets
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • 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.
  • Active central nervous system (CNS) metastases
  • Treatment with any investigational drug within 28 days prior to registration.

Other exclusion criteria as specified by drug manufacturer for specific investigational drug(s), e.g., cardiac disease, pulmonary disease.


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: Lisa Olmos 212-342-5162 cancerclinicaltrials@cumc.columbia.edu

Locations
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United States, New York
Columbia University Irving Medical Center Recruiting
New York, New York, United States, 10032
Contact: Lisa Olmos    212-342-5162    cancerclinicaltrials@cumc.columbia.edu   
Principal Investigator: Mark N Stein, MD         
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: March 26, 2020
Last Verified: March 2020

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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