| Eligibility |
Inclusion Criteria
Patients meeting all of the following criteria are considered for admission to the trial:
1. Diagnosis of UICC Stage IV mCRC, not eligible for local therapy
2. Women or men aged = 18 years, no upper age limit
3. ECOG performance status =2
4. 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.)
5. 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).
6. 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).
7. Written informed consent
8. 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:
1. Amenorrhea for at least 12 consecutive months without an alternative medical
cause following cessation of exogenous hormonal treatments.
2. Chemotherapy-induced menopause with >1 year interval since last menses
3. Surgical sterilisation
9. 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.
10. 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.
Exclusion Criteria
Patients meeting any of the following criteria are not eligible for the trial:
1. Patient with a known hypersensitivity to any of the excipients of sacituzumab
govitecan
2. Participation in other clinical trials involving an investigational drug(s) (Phases
1-4) or observation period of competing trials, respectively within 4 weeks prior to
study entry.
Patients participating in observational studies are eligible.
3. Taking medications that may interfere with SN-38 metabolism.
4. Have had a prior anticancer biologic agent within 2 weeks prior to enrollment or have
had prior chemotherapy, targeted therapy, or radiation therapy within 2 weeks prior to
enrollment AND have not recovered (ie, = Grade 2 is considered not recovered) from AEs
at the time of study entry.
5. Have not recovered (ie, = Grade 2 is considered not recovered) from AEs due to a
previously administered agent.
Note: patients with any grade neuropathy or alopecia are an exception to this
criterion and will qualify for the study.
Note: if patients received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.
6. Have an active second malignancy. Note: patients with a history of malignancy that
have been completely treated, with no evidence of active cancer for 3 years prior to
enrollment, or patients with surgically cured tumors with low risk of recurrence (eg,
nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in
situ, or similar) are allowed to enroll.
7. History of significant cardiovascular disease ( NYHA = III)
8. Clinical signs of active severe infection with or without requiring antibiotics.
- Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at
screening) with detectable viral load
- Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with
a history of HBV or HCV, patients with detectable viral loads will be excluded.
- Patients who test positive for hepatitis B surface antigen (HBsAg). Patients who
test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by
quantitative polymerase chain reaction (PCR) for confirmation of active disease.
- Patients who test positive for HCV antibody. Patients who test positive for HCV
antibody will require HCV RNA by quantitative PCR for confirmation of active
disease. Patients with a known history of HCV or a positive HCV antibody test
will not require a HCV antibody at screening and will only require HCV RNA by
quantitative PCR for confirmation of active disease.
9. Inadequate bone marrow, renal, and hepatic function defined by laboratory tests within
14 days prior to study treatment (growth factor support is not allowed within 14 days
prior to baseline labs; Hemoglobin <9 g/dl, Neutrophil count <1500/ l, Platelet count
<100000/l, Total bilirubin >1.5 times the institutional upper limit of normal (ULN,
except patients with Gilbert Syndrome, there >3.0 mg/dl), Aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) >2.5 ULN; subjects with documented liver
metastases may have an AST and ALT of >5.0 ULN and serum albumin <3 g/dl, Estimated
creatinine clearance calculated creatinine clearance <30 ml/minute according to the
Cockcroft and Gault formula)
10. Known microsatellite instable (MSI-H) / MMR-protein deficient (dMMR) colorectal
cancer.
11. Any medical or other condition which, in the opinion of the Investigator, causes the
subject to be medically unfit to receive sacituzumab govitecan, or unsuitable for any
other reason
12. Pregnancy and lactation
13. Inability of patient to understand character and consequences of the clinical trial
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