Purpose

This randomized phase II trial studies how well cabozantinib s-malate, crizotinib, savolitinib, 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, savolitinib, 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 giving cabozantinib s-malate, crizotinib, or savolitinib will work better in treating patients with kidney cancer compared to sunitinib malate.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
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 (must be obtained within 28 days prior to
registration)

- Absolute neutrophil count (ANC) >= 1,000/mcL (must be obtained within 28 days prior to
registration)

- Platelet count >= 75,000/mcL (must be obtained within 28 days prior to registration)

- Serum bilirubin =< 1.5 x institutional upper limits of normal (ULN) (must be obtained
within 28 days prior to registration)

- 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 (must be obtained within 28 days prior to registration)

- Serum creatinine must be =< 2 x the institutional ULN OR creatinine clearance (either
measured or calculated) must be > 30 mL/min (must be obtained within 28 days prior to
registration)

- 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

- Due to the unknown effects of the study drugs, patients must not be pregnant or
nursing; women/men of reproductive potential must have agreed to use an effective
contraceptive method while receiving study drug and for three months after last dose
of study drug; 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 because of the potential for pharmacokinetic interactions with
cabozantinib, crizotinib, savolitinib or sunitinib; in addition these patients are at
increased risk of lethal infections when treated with marrow suppressive therapy;
appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated

- 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

- As a part of the OPEN registration process the treating institution's identity is
provided in order to ensure that the current (within 365 days) date of institutional
review board approval for this study has been entered in the system.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: Sunitinib
    Given PO
  • 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
    Given PO
  • Drug: Cabozantinib S-malate
    Given PO
    Other names:
    • BMS-907351
    • Cabometyx
    • Cometriq
    • XL184
Experimental
Arm III (crizotinib closed to accrual 12/5/18)
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
Experimental
Arm IV (savolitinib closed to accrual 12/5/18)
Patients receive savolitinib PO on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Savolitinib
    Given PO
    Other names:
    • AZD6094
    • HMPL-504

Recruiting Locations

University of Texas Medical Branch
Galveston, Texas 77555-0565
Contact:
Site Public Contact
409-772-1950
clinical.research@utmb.edu

UTMB Cancer Center at Victory Lakes
League City, Texas 77573
Contact:
Site Public Contact
800-917-8906

More Details

NCT ID
NCT02761057
Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Study Contact

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.

TRANSLATIONAL 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. As of 12/5/18, patients will only be randomized to Arm I or Arm II.

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 (CLOSED TO ACCRUAL 12/5/18): Patients receive crizotinib PO twice daily (BID) on days 1-42.

ARM IV (CLOSED TO ACCRUAL 12/5/18): Patients receive savolitinib 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.