Traitments for refractory metastatic colorectal stable cancer.

Phase 1

• Conditions: TREATMENT FOR REFRACTORY METASTATIC MICROSATELLITE STABLE COLORECTAL CANCER; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001096-20-BE
• Lead Sponsor: Cliniques universitaires Saint-Luc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-30
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

1. Male or female = 18 years at time of study entry
2. Histologically proven metastatic colorectal adenocarcinoma, refractory to standard chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan) and anti-EGFR treatment (only for RAS WT tumor).
a. Patients who are received prior anti-angiogenic therapy (e.g, bevacizumab, aflibercept) are eligible
b. Patients must have had documented disease progression within 3 months of the last systemic therapy administration
c. Patients who were intolerant to prior systemic oxaliplatin-based chemotherapy regimens are eligible if there is documented evidence of
clinically significant intolerance despite adequate supportive measures.
d. For patients who had disease recurrence within 6 months of completing adjuvant chemotherapy, the adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease
3. MSS tumor, BRAF V600E WT tumor.
4. Measurable disease according RECIST 1.1
5. Availability of protocol required screening tumor and blood samples:
Metastases must be accessible for sequential biopsies. Patient must consent
for metastasis biopsies
6. ECOG performance status of 0 or 1
7. Adequate normal organ and marrow function
For women who are not postmenopausal (= 12 months of non-therapyinduced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly efficient methods of contraception, including at least one method
with a failure rate of < 1% per year, during the treatment period and for at
least 6 months after the last dose of treatment. Examples of contraceptive
methods with a failure rate of < 1% per year include bilateral tubal ligation,
male sterilization, established, proper use of hormonal contraceptives that
inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper
IUDs. The reliability of sexual abstinence should be evaluated in relation to
the duration of the clinical trial and the preferred and usual lifestyle of the
patient Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception. Barrier methods must always be supplemented with the use of a spermicide.
9. Patients who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result prior to initiation of study drug
10. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
11. A life expectancy of at least 4 months.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

1.BRAF V600E mutated tumor, MSI-High tumor
2. Patient has not received all of the standard chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan)
3.Previous treatment with regorafenib or TAS-102 (trifluridine/tipiracil)
4. Patients not consent for metastasis biopsy.
5. Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment.
6. Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry.
a. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be
treated prior to start of study treatment.
b. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis
that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to the start
of study treatment.
7. Active or untreated CNS metastases are excluded. Patients with treated and asymptomatic CNS metastases are eligible with some criteria.
8. Any previous treatment with a PD1 or PD-L1 inhibitor (including avelumab), CD137 agonists or anti-CTLA4
9. Participation in another clinical study with an investigational product for any other indication until 4 weeks before study participation.
10. Receipt of the last dose of anti-cancer therapy (chemotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) = 21 days prior to the first dose of study drug.
11. History of another primary malignancy except for exceptions (see protocol)
12. Any prior Grade =3 immune-related adverse event (irAE) while receiving anyprevious immunotherapy agent, or any unresolved irAE >Grade 1
13. Current or prior use of immunosuppressive medication within 28 days beforethe first dose of avelumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
14. Treatment with systemic immunostimulatory agents (including but not limitedto interferons or IL-2) within 4 weeks or five half-lives of the drug(whichever is shorter) prior to start the study treatment.
15. Receipt of live attenuated vaccination within 30 days prior first avelumab planned administration.
16. Mean QT interval corrected for heart rate (QTc) =470 ms
17. Active or prior documented autoimmune disease within the past 2 years.
18. Active or prior documented inflammatory bowel disease.
19. History of idiopathic pulmonary fibrosis, of primary immunodeficiency, of allogeneic organ transplant, of hypersensitivity to avelumab or any excipient, of hypersensitivity or unacceptable toxicity to cetuximab (anaphylactic reaction) or irinotecan or any excipient.
20. History of primary immunodeficiency, of allogeneic organ transplant, of hypersensitivity to avelumab or any excipient, of hypersensitivity to avelumab or any excipient.
21. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis B, hepatit

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified