| Eligibility |
Inclusion Criteria:
1. Able and willing to provide written informed consent and to comply with the clinical
study protocol
2. Age = 18 years
3. Histologically confirmed colorectal carcinoma
4. Peritoneal metastases (PCI=20 assessed during surgery), and histologically confirmed
as peritoneal carcinomatosis) eligible for cytoreductive surgery and HIPEC treatment
that reaches CC-0 at the end of the surgical procedure
5. AEs recovered to at least grade 1 from the effects (excluding alopecia) of any prior
medical therapy for malignancy at time of first administration of Radspherin®
6. ECOG Performance Status Score of 0 - 1
7. Adequate renal function
- Creatinine = 1.8 mg/dl (159 µmol/l) and
- Calculated creatinine clearance using the Cockcroft-Gault formula = 45 ml/min, or
- Measured creatinine clearance = 45 ml/min
8. Adequate hepatic function
- Serum bilirubin <1.5 x upper limit of normal (ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) = 3 x ULN
9. Adequate bone marrow function:
- Absolute neutrophil count (ANC) = 1.5 x 109/l
- Platelets = 100 x 109/l
- Haemoglobin = 9 g/dL
10. Adequate coagulation tests: INR = 1.5 x ULN
11. For females of childbearing potential, a negative pregnancy test must be documented
prior to enrolment
12. For females of childbearing potential; agreement to use at least one of the following
highly effective (failure rate<1%) methods of contraception during the treatment
period and for at least 12 months after the last dose of IMP:
- Total abstinence (when this is in line with the preferred and usual lifestyle of
the subject), periodic abstinence (e.g.: calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
enrolment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow-up hormone level assessment
- Male sterilization (at least 6 months prior to enrolment). The vasectomized male
partner should be the sole partner of the subject
- Use of oral, (estrogen and progesterone), injected or implanted hormonal methods
of contraception or placement of an IUD or IUS, or other forms of hormonal
contraception that have comparable efficacy (failure rate <1%), for example
hormone vaginal ring or transdermal hormone contraception. In case of use of oral
contraception women should have been stable on the same pill for a minimum of 3
months before taking study treatment.
13. For non-sterile males who's female partner is of childbearing potential: agreement to
use condom during the treatment period and for at least 12 months after the last dose
of investigational medicinal product. The female partner should use at least one of
the following highly effective (failure rate<1%) methods of contraception during the
treatment period and for at least 12 months after the last dose of the investigational
medicinal product (IMP):
- Total abstinence (when this is in line with the preferred and usual lifestyle of
the subject), periodic abstinence (e.g.: calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
enrolment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow-up hormone level assessment
- Use of oral, (estrogen and progesterone), injected or implanted hormonal methods
of contraception or placement of an intrauterine device (IUD) or intrauterine
system (IUS), or other forms of hormonal contraception that have comparable
efficacy (failure rate <1%), for example hormone vaginal ring or transdermal
hormone contraception. In case of use of oral contraception women should have
been stable on the same pill for a minimum of 3 months before taking study
treatment.
Note: Male sterilization must have been performed at least 6 months prior to enrolment. A
condom is required for all sexually active male subjects during the treatment period and
for at least 12 months after the last dose.
• Agree to refrain from donating sperm for the entire treatment period and for up to 12
months after the last dose.
Exclusion Criteria:
1. Peritoneal metastasis originating from appendix vermiformis. Other synchronous
visceral metastatic lesions in liver or lungs, symptomatic central nervous system
(CNS) metastases. Metastatic lymph nodes or thoracic lymph nodes
2. Resection or suture of the diaphragm (assessed during surgery)
3. Pregnant or lactating (nursing) women
4. Active infections requiring antibiotics and/or physician monitoring, or recurrent
fever >38.0°C associated with a clinical diagnosis of active infection
5. Active liver disease with positive serology for active hepatitis B, hepatitis C or
known HIV
6. Administration of an investigational medicinal product within 28 days or at least 5
times the half-life
7. Concurrent administration of any other cancer therapy other within 4 weeks prior to,
and up to 4 weeks after the last study treatment
8. Another primary malignancy within the past 3 years (except for non-melanoma skin
cancer, cervical cancer in situ or in situ stage 1 synchronous endometrial cancer)
9. Concurrent congestive heart failure or prior history of New York Heart Association
(NYHA) class III/IV cardiac disease
10. Any condition or illness that, in the opinion of the Investigator or the medical
monitor, would compromise the safety of the subjects or interfere with the evaluation
of the safety of the IMP
11. In the Investigator's opinion not able to comply with study procedures. Any medical or
psychological condition that would preclude participation in the study or compromise
the ability to give informed consent
12. Known hypersensitivity to any of the excipients in the study drug
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