This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Cabozantinib-S-Malate, Crizotinib, Volitinib, or Sunitinib Malate in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02761057
First received: May 2, 2016
Last updated: September 13, 2017
Last verified: August 2017
  Purpose
This randomized phase II trial studies how well cabozantinib-s-malate, crizotinib, volitinib, or sunitinib malate work in treating patients with kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate, crizotinib, volitinib, and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition Intervention Phase
Stage III Renal Cell Cancer Stage IV Renal Cell Cancer Type 1 Papillary Renal Cell Carcinoma Type 2 Papillary Renal Cell Carcinoma Drug: Cabozantinib S-malate Drug: Crizotinib Other: Laboratory Biomarker Analysis Drug: Sunitinib Malate Drug: Volitinib Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Phase II Efficacy Assessment of Multiple MET Kinase Inhibitors (Cabozantinib [NSC #761968], Crizotinib [NSC #749005], Savolitinib [NSC #785348], and Sunitinib [NSC #736511]) in Metastatic Papillary Renal Carcinoma (PAPMET)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause; assessed up to 3 years ]
    A proportional hazards model will be used to evaluate each pair wise treatment comparison of PFS, adjusting for the two stratification factors as covariates in the model.


Secondary Outcome Measures:
  • Incidence of toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to 3 years ]
    Toxicity defined as any grade 3 or 4 non-hematologic toxicity.

  • Overall survival (OS) [ Time Frame: Up to 3 years ]
    The method of Kaplan and Meier will be used to estimate survival curves. The log-rank test will be used to compare OS between the 4 treatment arms.

  • Response rate (RR) [ Time Frame: Up to 3 years ]
    The Chi-Square test will be used to compare RR between the control arm of sunitinib malate and the MET inhibitor treatment arms.


Other Outcome Measures:
  • MET mutation rate [ Time Frame: Up to 3 years ]
    The hazard ratio between the MET inhibitor vs. sunitinib in those with versus without the mutation (i.e., the interaction) will be compared. RECIST response rate (confirmed and unconfirmed PR and CR) based on MET mutation/expression level will be compared using the chi-square test.


Estimated Enrollment: 180
Actual Study Start Date: April 5, 2016
Estimated Primary Completion Date: March 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (sunitinib malate)
Patients receive sunitinib malate PO on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Sunitinib Malate
Given PO
Other Names:
  • SU011248
  • SU11248
  • sunitinib
  • Sutent
Experimental: Arm II (cabozantinib-s-malate)
Patients receive cabozantinib-s-malate PO on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Drug: Cabozantinib S-malate
Given PO
Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL184
Other: Laboratory Biomarker Analysis
Correlative studies
Experimental: Arm III (crizotinib)
Patients receive crizotinib PO BID on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Drug: Crizotinib
Given PO
Other Names:
  • MET tyrosine kinase inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori
Other: Laboratory Biomarker Analysis
Correlative studies
Experimental: Arm IV (volitinib)
Patients receive volitinib PO on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Volitinib
Given PO
Other Names:
  • AZD6094
  • HMPL-504
  • SAVOLITINIB

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare progression-free survival (PFS) in patients with metastatic papillary renal cell carcinoma (mPRCC) treated with sunitinib malate (sunitinib) to PFS in patients with mPRCC treated with MET kinase inhibitors.

SECONDARY OBJECTIVES:

I. To compare Response Evaluation Criteria in Solid Tumors (RECIST) response rate (RR; defined as the combined rate of confirmed and unconfirmed partial response [PR] and complete response [CR]) in patients with mPRCC treated with sunitinib to RR in patients treated with putative MET inhibitors.

II. To compare overall survival (OS) in patients with mPRCC treated with sunitinib to OS in patients with mPRCC treated with putative MET inhibitors.

III. To compare the safety profile of sunitinib and putative MET inhibitors in patients with mPRCC.

TERTIARY OBJECTIVES:

I. To evaluate the prognostic and predictive value of MET mutations, MET copy number or other markers of MET signaling in patients with mPRCC treated with putative MET inhibitors.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive sunitinib malate orally (PO) on days 1-28.

ARM II: Patients receive cabozantinib-s-malate PO on days 1-42.

ARM III: Patients receive crizotinib PO twice daily (BID) on days 1-42.

ARM IV: Patients receive volitinib PO on days 1-42.

In all arms, courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed papillary histology renal cell carcinoma which is metastatic or locally advanced disease not amenable to surgical resection; (NOTE: a designation of type I or type II should be made by the local pathologist if possible); mixed histologies containing type I or type II will be allowed provided that they contain >= 50% of the papillary component
  • Patients must also have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension; disease X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; if there is clinical suspicion for bone metastases at the time of enrollment (at the discretion of the investigator), bone scan should be performed at baseline (within 42 days prior to registration); all disease must be assessed and documented on the Baseline Tumor Assessment form
  • Patients with a history of treated brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)
  • Patients must not have cavitating pulmonary lesions; patients must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
  • Patients may have received prior surgery; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery
  • Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib); if a patient develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic renal cell carcinoma (RCC); if a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC; patients may have also received prior immunotherapy; patients must not have received a MET/hepatocyte growth factor (HGF) inhibitor or sunitinib as prior therapy; at least 14 days must have elapsed since completion of prior systemic therapy; patients must have recovered from all associated toxicities at the time of registration
  • Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 14 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
  • Patients must not be taking, nor plan to take while on protocol treatment, strong CYP3A4 inhibitors (e.g. boceprevir, cobicistat, danoprevir, elvitegravir/RIT, fluvoxamine, indinavir, itraconazole, ketoconazole, lopinavir/RIT, nefazodone, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, tipravavir/RIT, or voriconazole); strong CYP3A4 inducers (e.g. avasimibe, phenytoin, rifampin, rifabutin); potent inhibitors of CYP1A2 (e.g. ciprofloxacin); and/or drugs known to be CYP3A4 substrates with a narrow therapeutic range (e.g., diergotamine, ergotamine) within 14 days prior to randomization; moderate inhibitors or inducers of isoenzyme CYP3A4 should be avoided, but if necessary can be used with caution
  • Patients must not be receiving or planning to receive any other investigational agents
  • Patients must have a complete physical examination and medical history within 28 days prior to registration
  • Patients must have a Zubrod performance status of 0 - 1
  • White blood cell count (WBC) >= 2,000/mcL
  • Absolute neutrophil count (ANC) >= 1,000/mcL
  • Platelet count >= 75,000/mcL
  • Serum bilirubin =< 1.5 x institutional upper limits of normal (ULN)
  • Serum transaminase (serum glutamic oxaloacetic transaminase [SGOT]/aspartate aminotransferase [AST] and serum glutamate pyruvate transaminase [SGPT]/alanine aminotransferase [ALT]) must be =< 2.5 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT/SGPT) must be =< 5 x the institutional ULN
  • Serum creatinine must be =< 2 x the institutional ULN OR creatinine clearance (either measured or calculated) must be > 30 mL/min
  • Patients must not have any clinical evidence of congestive heart failure (CHF) (specifically, New York Heart Association [NYHA] class III [moderate] or class IV [severe]) at the time of registration; baseline echocardiogram within 28 days of registration must demonstrate an ejection fraction (EF) >= 50%; patients must have corrected QT (QTc) interval < 500 msec on prestudy electrocardiogram (EKG) and no known history of congenital long QT syndrome; patients must not have experienced unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke (transient ischemic attack [TIA] or other ischemic event) within 3 months prior to registration and not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 6 months of registration; prestudy EKG must be obtained within 28 days prior to registration
  • Baseline urinalysis should show urine protein < 3+ and must be obtained within 28 days prior to registration; if urine protein is 3+ or greater, then urine protein by 24 hour collection must show less than 3 grams of protein
  • Patients must not have inadequately controlled hypertension; patients must have documented blood pressures of systolic blood pressure (SBP) < 150 and diastolic blood pressure (DBP) < 90 within 14 days of starting randomization; blood pressure medications (any number) are permitted
  • Patients must be able to take oral medications (i.e., swallow pills whole); patients must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures that could in the opinion of the treating investigator affect absorption, or active peptic ulcer disease; patients with intractable nausea or vomiting are not eligible
  • Patients must not have had any clinically-significant GI bleeding within 6 months prior to registration and patients must not have a GI disorder which (at the discretion of the investigator) bears a high risk of perforation or fistula; examples of this include (but are not limited to) Crohn's disease or tumor with transmural extension through the gastrointestinal lining
  • Patients must not have had hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months prior registration
  • Patients must not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior to registration
  • Patient's baseline imaging must not indicate the presence of tumor invading or encasing any major blood vessels
  • Patients must not have any unresolved wounds from previous surgery
  • Albumin, alkaline phosphatase, bicarbonate, blood urea (BUN), chloride, glucose, phosphorus, and total protein must be assessed within 28 days of registration
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for 3 years; men receiving active surveillance for prostate cancer may also be enrolled
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients must have tissue available and be willing to submit for independent pathologic review in order to classify type I versus type II papillary disease
  • Patients must be offered the opportunity to participate in specimen banking for future translational medicine studies
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  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: NCT02761057

  Show 484 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sumanta Pal Southwest Oncology Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02761057     History of Changes
Other Study ID Numbers: NCI-2015-01707
NCI-2015-01707 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1500 ( Other Identifier: SWOG )
S1500 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
Study First Received: May 2, 2016
Last Updated: September 13, 2017

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Adenocarcinoma
Urologic Diseases
Sunitinib
Crizotinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 19, 2017