A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer

Exclusion Criteria

• •2.1.2.1 Patients who are receiving any other investigational agents for treatment of their kidney cancer.
• •2.1.2.2 History of allergic reactions attributed to compounds of similar chemical or biologic composition to Capmatinib (INC280). Excipients in the current formulation include microcrystalline cellulose, mannitol, sodium starch glycolate, magnesium stearate and colloidal silicon dioxide
• •2.1.2.3 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or potentially affect the interpretation of study data.
• •2.1.2.4 Subjects with significant or uncontrolled cardiovascular disease (e.g., uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months prior to starting study treatment or heart attack within 12 months prior to starting study treatment
• •2.1.2.5 Patients receiving any medications that are known to be strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4), or sensitive substrates of CYP3A4, cytochrome P450 1A2 (CYP1A2), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 2C19 (CYP2C19) or P-glycoprotein (P-gp) with a narrow therapeutic index.
• •2.1.2.6 Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring \> 5 mg/day of dexamethasone (or equivalent) to control CNS disease.
• •Note: Patients with controlled CNS metastases are allowed. Radiotherapy or surgery for CNS metastases must have been completed \>2 weeks prior to study entry. Patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging. Steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entry.
• •2.1.2.7 Patients with greater than or equal to Grade 2 neuropathy.
• •2.1.2.8 Treatment with proton pump inhibitors within 3 days prior to study entry. If continued use of gastrointestinal (GI) prophylaxis is required, the patient will be switched to an appropriate Histamine H2-receptor antagonists (H2) with appropriate counsel and caution.
• •2.1.2.9 Currently receiving any prohibited medications including vitamins and herbal Supplements.
• •2.1.2.10 Major surgery within 4 weeks prior to initiating treatment, excluding the placement of vascular access.
• •2.1.2.11 The subject has not recovered to baseline, Common Terminology Criteria for Adverse Events (CTCAE) less than or equal to Grade 1 from toxicity due to all prior therapies for RCC or to a level permitted under other sections of the eligibility criteria except alopecia and other non-clinically significant adverse events (AEs).
• •2.1.2.12 Any other condition that would, in the Investigators judgment, contraindicate participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
• •2.1.2.13 Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (\> 30 mIU/mL). Laboratory values \>5 mIU/mL, but \<30 mIU/mL should be repeated in 48 hours.
• •2.1.2.14 Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months days after stopping study drug. Highly effective contraception methods include:
• •Total abstinence or
• •Male or female sterilization or
• •Combination of any two of the following (a+b or a+c or b+c):
• •1. Use of oral, injected or implanted hormonal methods of contraception
• •2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
• •3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
• •2.1.2.15 Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
• •2.1.2.16 Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Capmatinib (INC280).
• •2.1.2.17 Prior invasive malignancy of other histology currently requiring treatment.