A Phase 2 Trial of SCO-101 in combination with FOLFIRI for Patients with Metastatic Colorectal Cancer (mCRC) with acquired Resistance to FOLFIRI

Prior treatment

• Concurrent chemotherapy, radiotherapy, or other investigational drugs during study period.
• Other medications or conditions that in the Investigator’s opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results.   Other severe medical conditions, including serious heart disease, unstable diabetes, uncontrolled hypercalcemia, clinically active infections or previous organ transplants. Participation in another clinical trial with experimental medication within 30 days prior to registration.
• Malabsorption syndrome or previous surgeries with resection of the stomach or small intestine, whereby absorption of SCO-101 may be affected.  This includes patients with ileostomy.
• Clinical symptoms of CNS metastases requiring steroids.
• Clinical significant (i.e. active) cardiovascular disease: • Stroke within ≤ 6 months prior to day 1   • Transient ischemic attach (TIA) within ≤ 6 months prior to day 1   • Myocardial infarction within ≤ 6 months prior to day 1   • Unstable angina   • New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF)   • Serious cardiac arrhythmia requiring medication

Other illness

• Known hypersensitivity to SCO-101, irinotecan, 5-FU or structurally similar drugs (e.g. capecitabine), leucovorin and G-CSF.
• Any active infection requiring parenteral or oral antibiotic treatment.
• Known HIV positivity.
• Known active hepatitis B or C.
• Mental status is not fit for clinical study or CNS disease including symptomatic epilepsy.

Other

• Pregnant women or women who are breastfeeding.
• Patients with known Dihydropyrimidine dehydrogenase (DPD) deficiency.
• Difficulty in swallowing tablets.

• Ability to understand and willingness to provide written informed consent before any trial-related activities.
• Recovered to Grade 1 or less from prior surgery or acute toxicities of prior radiotherapy or treatment with cytotoxic or biologic agents.
• ≥ 2 weeks must have elapsed since any prior surgery.
• Adequate conditions as evidenced by the following clinical laboratory values:   • Absolute neutrophils count (ANC) ≥ 1.5 x 109/L   • Hemoglobin ≥ 6.0 mmol/L   • Platelets ≥ 100 x 109 /L   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN*   • Total serum bilirubin ≤ 1.0 ULN**   • Alkaline phosphatase ≤ 2.5 x ULN*   • Normal kidney function defined by the centers with the method usually employed locally. i.e. either creatinine (≤ 1.5 ULN) or calculated creatinine clearance or eGFR within normal limits determined according to local standards • Adequate blood clotting function as defined by the International Normalized Ratio (INR) ≤ 1.5
• Life expectancy equal to or longer than 3 months.
• Sexually active males and females of child-producing potential must use highly effective contraception (intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) for the study duration and at least 6 months after the last dose of study drug.
• Signed informed consent.
• Patients are only eligible for inclusion if no further on label treatment alternatives are available, i.e: (a) They have progressed on all available standard treatments, and/or (b) are intolerant to all remaining standard treatments, and/or (c) decline treatment with all other standard treatments, and/or (d) if the patient according to the treating physicians cannot be offered further standard treatment for their cancer disease.
• Age 18 years or older.
• Histologically verified colorectal adenocarcinoma.
• Non-resectable mCRC in patients. A. Stage 1: with or without BRAF, RAS or known repair enzyme mutations / B. Stage 2: without known BRAF, RAS or repair enzyme mutations / C. Stage 3: with or without BRAF, RAS or repair enzyme mutations, actual status to be confirmed prior to enrollment
• Previous treatment and documented progressive disease with irinotecan and 5-FU (including 5-FU based analogs, e.g. capecitabine) based chemotherapy regimens (with or without antiangiogenetic and EGFR inhibitory biological treatment).
• Maximum reduction of 33% in prior dose of FOLFIRI.
• Previous treatment with an oxaliplatin-containing treatment regimen and no indication for re-challenge with oxaliplatin. The patient can have received oxaliplatin treatment before and/or after treatment with FOLFIRI.
• Stage 1 and 3 only: Evaluable disease by CT scan or MRI. / B. Stage 2 only: Measurable disease by CT scan or MRI, according to RECIST.
  • Performance status of ECOG ≤ 1.