Patient case: 35-year-old female with Colorectal cancer. Genetic variant: FGFR1 Amplification. Other conditions: None.

Clinical trial: Everolimus and OSI-906 for Patients With Refractory Metastatic Colorectal Cancer

Summary: The purpose of this study is to determine the maximum tolerated dose (MTD) of the combination of OSI-906 and everolimus for the treatment of patients with refractory metastatic colorectal cancer.


Eligibility: Inclusion Criteria:
  -  Metastatic cancer of the colon or rectum that has progressed on or for which the patient is intolerant to or not a candidate for: fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab.
  -  Testing for Kras mutation performed;Patients with mutated or wild type Kras are eligible.
  -  ECOG PS of 0-1
  -  Life expectancy of ≥ 3 months
  -  Adequate hematological function with ANC 1500, Platelets of 100,000, and hemoglobin of 9.0
  -  AST, ALT and Alk. Phos. ≤2.5 x ULN or ≤5 x ULN if known hepatic metastases and a total bilirubin ≤1.5 ULN
  -  Serum creatinine of ≤1.5 x ULN
  -  Fasting blood glucose <150 mg/dL
  -  Measurable disease according to RECIST 1.1
  -  Able to swallow whole pills
  -  INR ≤1.5 - Anticoagulation is allowed with LMW heparin
  -  Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN;If these thresholds are exceeded, the patient can be included after initiation of lipid lowering medication
  Exclusion Criteria:
  -  Patients who have received any cancer therapies <4 weeks or 5 half lives (whichever is shorter) of initiating study therapy
  -  Treatment with any investigational drug ≤ 4 weeks, or 5 half-lives of the drug, whichever is shorter
  -  Patients who require coumadin for anticoagulation
  -  Patients who have had major surgery or significant traumatic injury ≤4 weeks of the of study treatment
  -  Minor surgery (with the exception of port placement) must be completed ≤ 7days prior to study therapy
  -  Previous treatment with an IGFR inhibitor or MTOR Inhibitor
  -  Chronic, systemic treatment with corticosteroids or another immunosuppressive agent
  -  Patients with QTc interval >450ms
  -  Patients who require drugs that can prolong QTc.
  -  Patients with congenital long QT syndrome, history of ventricular tachycardia, or ventricular fibrillation, or Torsades de Pointes with bradycardia.
  -  Immunization with attenuated live vaccines within 1 week of beginning study therapy or during study period;Close contact to anyone that has received live virus vaccine should be avoided
  -  Meningeal or brain metastasis
  -  Other malignancies < 3 years, with the exception of adequately treated basal or squamous cell carcinomas of the skin, or carcinoma in situ of the cervix
  -  Patients with known HIV
  -  Patients with positive testing for hepatitis B or C
  -  Patients with risk factors for hepatitis must be tested for hepatitis viral loadHepatitis risk factors include the following:
  Lived in Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal, and Greece Any blood transfusions before 1990 Any IV drug use Any dialysis Household contact with a Hep B infected patient Mother had Hep B High-risk sexual activity Body piercing/tattoos
  -  History suggestive of hepatitis B
  -  Any severe or uncontrolled conditions that could affect their study participation such as:Severely impaired lung function;DCLO ≤ 50% of normal predicted value;O² Sat <88% at rest on room air
  -  Congestive Heart Failure of NYHA Class III or IV
  -  Unstable angina, symptomatic CHF, MI ≤ 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant heart disease
  -  CVA, TIA, angioplasty, or cardiac stenting <12 months
  -  Ventricular arrhythmia requiring medication
  -  Known history of diabetes and/or patients who require ongoing use of insulin or oral anti-hyperglycemic therapy
  -  Known liver disease
  -  Impairment of GI function or gastrointestinal disease that in may significantly alter the absorption of study drugs
  -  Concurrent treatment with drugs that are strong CYP3A4 inducers or moderate/strong CYP3A4 inhibitors
  -  Concurrent treatment with drugs that are strong CYP1A2 inhibitors or inducers Women who are pregnant or breastfeeding.
  -  Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements

Relevance to patient case: not relevant