Clinical Trials /

Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed

NCT02761057

Description:

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.

Related Conditions:
  • Papillary Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cabozantinib-S-Malate, Crizotinib, Volitinib, or Sunitinib Malate in Treating Patients With Locally Advanced or Metastatic Kidney Cancer
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2015-01707
  • SECONDARY ID: NCI-2015-01707
  • SECONDARY ID: S1500
  • SECONDARY ID: S1500
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT02761057

Conditions

  • Recurrent Renal Cell Carcinoma
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Type 1 Papillary Renal Cell Carcinoma
  • Type 2 Papillary Renal Cell Carcinoma

Interventions

DrugSynonymsArms
Cabozantinib S-malateBMS-907351, Cabometyx, Cometriq, XL184Arm II (cabozantinib-s-malate)
CrizotinibMET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, XalkoriArm III (crizotinib)
Sunitinib MalateSU011248, SU11248, sunitinib, SutentArm I (sunitinib malate)
VolitinibAZD6094, HMPL-504, SAVOLITINIBArm IV (volitinib)

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (sunitinib malate)ExperimentalPatients receive sunitinib malate PO on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
  • Sunitinib Malate
Arm II (cabozantinib-s-malate)ExperimentalPatients receive cabozantinib-s-malate PO on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
  • Cabozantinib S-malate
Arm III (crizotinib)ExperimentalPatients receive crizotinib PO BID on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
  • Crizotinib
Arm IV (volitinib)ExperimentalPatients receive volitinib PO on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
  • Volitinib

Eligibility 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; 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 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. ketoconazole, itraconazole, voriconazole, posaconazole,
             fluvoxamine, nefazodone, nelfinavir, ritonavir) and/or strong CYP3A4 inducers (e.g.
             phenytoin, rifampin, rifabutin) 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; 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 central 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure: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
Safety Issue:
Description:Toxicity defined as any grade 3 or 4 non-hematologic toxicity.
Measure:OS
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:RR
Time Frame:Up to 3 years
Safety Issue:
Description:The Chi-Square test will be used to compare RR between the control arm of sunitinib malate and the MET inhibitor treatment arms.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

April 20, 2017