Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01835158
First received: April 16, 2013
Last updated: August 19, 2014
Last verified: May 2014
  Purpose

This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread to nearby areas of the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate or sunitinib malate is more effective in treating patients with kidney cancer.


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: cabozantinib-s-malate
Drug: sunitinib malate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study Comparing Cabozantinib (NSC #761968) With Commercially Supplied Sunitinib in Patients With Previously Untreated Locally Advanced or Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The primary analysis will be based on the stratified log-rank statistic to compare the two treatment arms on PFS. The Kaplan-Meier product-limit estimator will be used to estimate PFS distributions.

  • Overall survival (OS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The primary analysis will be based on the stratified log-rank statistic to compare the two treatment arms on OS. The Kaplan-Meier product-limit estimator will be used to estimate OS distributions.


Secondary Outcome Measures:
  • Objective response rates [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The Fisher exact test will be used to compare the two treatment arms.

  • Proportion of patients with unacceptable treatment related grade 3 or higher toxicity for all patients assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The Fisher exact test will be used to compare the two treatment arms.


Other Outcome Measures:
  • High MET expression (total MET and phospho/MET) by IHC [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will determine if there is an association between high MET expression and better PFS and OS.


Estimated Enrollment: 150
Study Start Date: July 2013
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (cabozantinib-s-malate)
Patients receive cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: cabozantinib-s-malate
Given PO
Other Names:
  • BMS-907351
  • Cometriq
  • XL184
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (sunitinib malate)
Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if patients with renal cancer treated with cabozantinib (cabozantinib-s-malate) will have improved progression-free survival compared to patients treated with sunitinib (sunitinib malate).

SECONDARY OBJECTIVES:

I. To determine whether the response rate of patients with renal cancer treated with cabozantinib will be higher when compared with patients treated with sunitinib.

II. To determine whether patients with renal cancer treated with cabozantinib will have an improved overall survival when compared with patients treated with sunitinib.

TERTIARY OBJECTIVES:

I. To determine whether renal cancer patients with high met proto-oncogene (MET) expression by immunohistochemistry (IHC) have improvement in progression-free survival compared to patients with low MET expression on both arms of this study.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cabozantinib-s-malate orally (PO) once daily (QD) for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic documentation: renal cell carcinoma with some component of clear cell histology; histologic documentation of metastatic disease is not required
  • Stage: locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma (RCC) (equivalent to stage IV RCC, according to American Joint Committee on Cancer [AJCC] staging)
  • Eligible patients must be intermediate/poor risk, per the International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (Heng) criteria defined as one or more of the following six factors:

    • Time from diagnosis of RCC to systemic treatment < 1 year
    • Hemoglobin < the lower limit of normal (LLN)
    • Corrected calcium > the upper limit of normal (ULN)
    • Karnofsky performance status < 80%
    • Neutrophil count > ULN
    • Platelet count > ULN
  • No radiographic evidence of cavitating pulmonary lesion(s)
  • No tumor in contact with, invading or encasing any major blood vessels
  • No evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days prior to registration
  • No prior systemic treatment for RCC; supportive therapies such as bisphosphonates (zoledronic acid) or denosumab are permitted
  • Patients must not have had a major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; however, patients who have had a nephrectomy may be enrolled 4 weeks after surgery, providing there are no wound-healing complications; the following are not considered to be major procedures: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures
  • Radiation:

    • To the brain, thoracic cavity, abdomen, or pelvis must be completed at least 90 days before registration;
    • To bone must be completed at least 14 days before registration; and
    • To any other sites must be completed at least 28 days before registration In all cases, there must be complete recovery and no ongoing complications from prior radiation therapy
  • No chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors; patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration
  • Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria; lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan
  • No active brain metastases; patients with treated, stable brain metastases for at least three months are eligible as long as they meet the following criteria:

    • Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or CT); (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to registration are not eligible
    • Baseline brain imaging (MRI/CT) is required
  • No serious non-healing wound, ulcer, or bone fracture within 28 days prior to registration
  • No arterial thrombotic events within 6 months prior to registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the 6 months prior to registration, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection), or any other arterial thrombotic event are ineligible
  • No history of pulmonary embolism or untreated deep venous thrombosis (DVT) within 6 months prior to registration; note: patients with recent DVT who have been treated with therapeutic anticoagulation with low molecular weight heparin for at least 6 weeks are eligible; patients receiving therapeutic warfarin (> 2 mg/day) are not eligible; patients on warfarin may be switched to low molecular weight heparin at the discretion of the treating physician
  • No inadequately controlled hypertension (defined as a blood pressure of >= 150 mmHg systolic and/or >= 90 mmHg diastolic), or any prior history of hypertensive crisis or hypertensive encephalopathy
  • No New York Heart Association (NYHA) class >= 2 congestive heart failure
  • Ejection fraction on echocardiogram (Echo) or multi gated acquisition scan (MUGA) > 50%
  • No corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
  • No history of congenital QT syndrome
  • No unstable cardiac arrhythmia within 6 months prior to registration
  • No evidence of any of the following:

    • Clinically-significant gastrointestinal bleeding within 6 months before registration; or
    • Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before registration; or
    • Any other signs indicative of pulmonary hemorrhage within 3 months before registration
  • No history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 6 months prior to registration and complete healing/resolution prior to registration; no percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months prior to registration
  • No active peptic ulcer disease, within 28 days before registration
  • No inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis within 28 days before registration
  • No malabsorption syndrome within 28 days before registration
  • No untreated hypothyroidism; patients with hypothyroidism on therapy are required to have thyroid stimulating hormone (TSH) within normal limits
  • No radiologic or clinical evidence of pancreatitis
  • No history of organ transplant
  • Patients with active infection requiring systemic treatment within 28 days prior to registration are not eligible
  • Patients who are pregnant or nursing are not eligible; women of child bearing potential must have a negative serum or urine pregnancy test within 16 days prior to registration; women of child-bearing potential include:

    • Any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months)
    • Women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35m IU/mL
    • Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)
  • Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2
  • Archival tissue must be available for submission, though it is optional for patients to choose to participate in the correlative sub studies
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelet count >= 100,000/uL
  • Hemoglobin >= 9 g/dL; patients may not have had a transfusion within 7 days prior to screening assessment
  • Total bilirubin =< 1.5 x upper limits of normal
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Albumin >= 2.8 g/dL
  • Serum creatinine =< 1.5 x ULN, OR calculated creatinine clearance >= 30 mL/minute (modified Cockroft and Gault formula)
  • Urine protein to creatinine (UPC) ratio < 1.0; if UPC >= 1, then a 24-hour urine protein must be assessed; eligible patients must have a 24-hour urine protein value < 1 g
  • Total serum calcium < 12 mg/dL
  • International normalized ratio (INR) =< 1.2 x ULN; subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
  • TSH within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01835158

  Show 452 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Toni Choueiri Alliance for Clinical Trials in Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01835158     History of Changes
Other Study ID Numbers: NCI-2013-00820, NCI-2013-00820, CALGB-A031203, A031203, A031203, U10CA031946, U10CA180821
Study First Received: April 16, 2013
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014