Avelumab and Cetuximab in Combination With FOLFOX in Patients With Previously Untreated Metastatic Colorectal Cancer - The Phase II AVETUX-CRC Trial.

NCT03174405 | Completed Phase 2 DMC

• 3 other identifiers: AIO-KRK-02162016-004434-26MS100070_0065
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

AVETUX is a single arm multicentric phase II investigator initiated trial conducted by the Arbeitsgemeinschaft Internistische Onkologie (AIO) in 11 German sites in patients with previously untreated RAS/BRAF wildtype mCRC independent of MSI status.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival Rate (PFS) @ 12 months

  PFS according to RECIST 1.1 at 12months of treatment

  during 12 months of treatment

Secondary Outcomes (5)

• Safety

  21 months

• Response Rate (RR)

  4 years

• Progression Free Survival (PFS)

  4 years

• Overall survival (OS)

  4 years

• Translational research

  48 months

Study Arms (1)

AVELUMAB

EXPERIMENTAL

Drug: Avelumab

Interventions

Avelumab DRUG

All eligible patients will receive cetuximab and mFOLFOX6 combined avelumab from the second cycle onwards. Cetuximab at a dose of 250 mg/m2 IV over 60 to 90 min (day 1 and 8) (first dose 400mg/m2) mFOLFOX6 (administration according to local standard) Oxaliplatin at a dose of 85 mg/m2 IV (day 1) 5-FU 400 mg/m2 IV bolus (day 1) LV at a dose of 400 mg/m2 iv (day 1) 5-FU at a dose of 2400 mg/m2 IV (day 1-3) Avelumab at a dose of 10mg/kg IV over 60 to 90 min (day 1 from cycle 2 onwards)

AVELUMAB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed, previously untreated RAS and BRAF wildtype, MSI or MSS metastatic 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. 10. 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 90 days after avelumab treatment and 6 month after standard chemotherapy.
• \. At least 6 months after completion of adjuvant chemotherapy. 12. Written informed consent 13. 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

You may not qualify if:

• All subjects with known brain metastases, except those meeting the following criteria:
• Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment
• 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)
• 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:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• 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:
• 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
• 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 10. 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.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead

Study Sites (1)

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Related Publications (2)

• Tintelnot J, Ristow I, Sauer M, Simnica D, Schultheiss C, Scholz R, Goekkurt E, von Wenserski L, Willscher E, Paschold L, Lorenzen S, Riera-Knorrenschild J, Depenbusch R, Ettrich TJ, Dorfel S, Al-Batran SE, Karthaus M, Pelzer U, Hinke A, Bauer M, Massa C, Seliger B, Wickenhauser C, Bokemeyer C, Hegewisch-Becker S, Binder M, Stein A. Translational analysis and final efficacy of the AVETUX trial - Avelumab, cetuximab and FOLFOX in metastatic colorectal cancer. Front Oncol. 2022 Dec 20;12:993611. doi: 10.3389/fonc.2022.993611. eCollection 2022.

  PMID: 36605436 DERIVED

• Stein A, Simnica D, Schultheiss C, Scholz R, Tintelnot J, Gokkurt E, von Wenserski L, Willscher E, Paschold L, Sauer M, Lorenzen S, Riera-Knorrenschild J, Depenbusch R, Ettrich TJ, Dorfel S, Al-Batran SE, Karthaus M, Pelzer U, Waberer L, Hinke A, Bauer M, Massa C, Seliger B, Wickenhauser C, Bokemeyer C, Hegewisch-Becker S, Binder M. PD-L1 targeting and subclonal immune escape mediated by PD-L1 mutations in metastatic colorectal cancer. J Immunother Cancer. 2021 Jul;9(7):e002844. doi: 10.1136/jitc-2021-002844.

  PMID: 34315821 DERIVED

Related Links

• Homepage of the AIO (Arbeitsgemeinschaft Internistische Onkologie in der Deutschen Krebsgesellschaft e.V.)

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Alexander Stein, PD Dr.

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 2, 2017
• Study Start: July 17, 2017
• Primary Completion: July 16, 2020
• Study Completion: July 16, 2021
• Last Updated: September 29, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)