A Randomized, Open Label, Multicenter Phase II/III Trial of Sacituzumab Govitecan Compared to Standard of Care in Metastatic, Refractory Colorectal Cancer Patients
This is a Phase: II/III, open-label, multicenter (at least four centers in Germany) study of Sacituzumab Govitecan (SG) in metastatic colorectal cancer patients who are refractory to at least two lines of standard of care chemotherapy and not eligible for local therapy. There is no upper limit in the previous therapy lines. Patients must have documented progression or intolerability to combination chemotherapy including 5-fluoruacil or its prodrugs and derivates, Oxaliplatin and Irinotecan or a combination of the aforementioned. Previous biologicals/antibodies/small molecules including anti-EGFR and anti-VEGF directed therapies are allowed but not mandatory to meet eligibility. Trifluridin/Tipiracil (TAS102) or Regorafenib are allowed but not mandatory as previous therapies for PART I and PART II of the trial. All patients must have a documented Irinotecan-free interval of at least 6 months to be eligible for the study. The study consists of two parts: PART I: a single arm run in phase, treating 20 patients with Sacituzumab Govitecan (SG) PART II: a 1:1 randomized open label phase, comparing 30 patients treated with SG vs. 30 patients treated according to Physicians Choice (PhC). Crossover to the experimental arm (SG) is allowed in case of progression in the standard arm (PhC). PART II will only be started if significant clinical efficacy and activity is observed in PART I.
∙ Patients meeting all of the following criteria are considered for admission to the trial:
• Diagnosis of UICC Stage IV mCRC, not eligible for local therapy
• Women or men aged ≥ 18 years, no upper age limit
• ECOG performance status ≤2
• Patients must have failed standard therapy or were intolerable towards standard therapy which must include fluoropyrimidine, oxaliplatin and irinotecan. (Targeted therapies (in combination with chemotherapy) including antiangiogenic monoclonal antibody/fusion protein/small molecule (e.g. bevacizumab, aflibercept, ramucirumab) and anti-EGFR antibody (e.g. Cetuximab, Panitumumab) are allowed as previous therapies.)
• No Irinotecan treatment within the last 6 months. Patients that received Irinotecan treatment more than 6 months prior to inclusion, must have been responsive to Irinotecan induction therapy (i.e., patients previously exposed to induction chemotherapy containing irinotecan must have presented CR or PR or else SD at least 3 months or at initial response assessment).
• At least one measurable lesion according to RECIST 1.1 that can be accurately assessed at screening by computed tomography or magnetic resonance imaging and is suitable for repeated assessment or available CT scan of thorax and abdomen not older than 30 days before start of treatment (day 1 of cycle 1).
• Written informed consent
• Non-pregnant and non-nursing women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to start of study treatment. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile.
• Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
• Post-menopausal or evidence of non-childbearing status is defined within this clinical trial:
‣ Amenorrhea for at least 12 consecutive months without an alternative medical cause following cessation of exogenous hormonal treatments.
‣ Chemotherapy-induced menopause with \>1 year interval since last menses
‣ Surgical sterilisation
• WOCBP are to be advised using two effective methods of birth control to avoid pregnancy throughout the study and for at least 6 months after the last dose of IMP. This includes effective contraception methods that can achieve a failure rate of less than 1% per year (e.g. hormonal contraceptive and condom, IUD/IUS and condom) or sterilization, resulting in a failure rate less than 1% per year.
⁃ Fertile men should not donate sperm and must be willing and able to use two effective methods of birth control (e.g latex condoms plus hormonal contraception in their partner) throughout the study and for at least 6 months after the last dose of IMP, if their sexual partners are WOCBP (acceptable methods see above). A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.