Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer.

Phase 1

• Conditions: metastatic colorectal cancer; MedDRA version: 20.0Level: PTClassification code 10010035Term: Colorectal cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004434-26-DE
• Lead Sponsor: AIO-Studien-gGmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12-23
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Patients with histologically confirmed, previously untreated RAS and BRAF wildtype, MSI or MSS metastastic colorectal cancer (primary tumor may be present)
• Patients with at least one measurable lesion acc. to RECIST v1.1
• ECOG Performance status = 1
• Life expectancy > 3 months
• Age = 18 years.
• Haematologic function as follows: ANC = 1.5 x 10^9/L, platelets = 100 x10^9/L, hemoglobin = 9 g/dl or 5.59 mmol/l
• Adequate liver function as measured by serum transaminases (AST & ALT) = 2.5 x ULN (in case of liver metastases < 5 x ULN) and total bilirubin = 1.5 x ULN. Patients with known Gilbert disease who have serum bilirubin level = 3 × ULN may be enrolled.
• Adequate renal function: serum creatinine = 1.5 x ULN
• Negative serum pregnancy test at screening for women of childbearing potential.
• Highly effective contraception for both male and female subjects if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 30 days after avelumab treatment.
• At least 6 months after completion of adjuvant chemotherapy.
• Written informed consent
• Ability to comply with the protocol for the duration of the study, including hospital/office visits for treatment and scheduled follow-up visits and examinations

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 21
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion Criteria

• Malignancies other than disease under study within 5 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
• All subjects with known brain metastases, except those meeting the following criteria:
o Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment
o No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
o Subjects must be either off steroids or on a stable or decreasing dose of <10mg daily prednisone (or equivalent)
• Prior organ transplantation, including allogeneic stem-cell transplantation
• Significant acute or chronic infections including, among others:
o Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
o Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent (Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible)
• Concomitant treatment with corticosteroids or other immunosuppressants, besides treatment of brain metastases as mentioned in criteria 2 or:
o Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses = 10 mg or 10 mg equivalent prednisone per day
o Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI-CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Pregnancy or lactation
• Known alcohol or drug abuse
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable.
• All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma, colitis and pneumonitis), which, in the opinion of the Investigator, might impair the subject’s tolerance of trial treatment
• Any psychiatric condition that would prohibit the understanding or rendering of informed consent
• Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
• Any approved anticancer therapy, including chemotherapy, hormonal therapy or radiotherapy, within 4 weeks prior to ini

Study & Design

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