Clinical Trials /

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

NCT03174405

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Avelumab and Cetuximab in Combination With FOLFOX in Patients With Previously Untreated Metastatic Colorectal Cancer - The Phase II AVETUX-CRC Trial.
  • Official Title: Avelumab and Cetuximab in Combination With FOLFOX in Patients With Previously Untreated Metastatic Colorectal Cancer - The Phase II AVETUX- Colorectal Cancer (CRC) Trial.

Clinical Trial IDs

  • ORG STUDY ID: AIO-KRK-0216
  • SECONDARY ID: 2016-004434-26
  • SECONDARY ID: MS100070_0065
  • NCT ID: NCT03174405

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
AvelumabAVELUMAB

Purpose

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.

Detailed Description

      The primary clinical objective is to determine the efficacy of a standard 1st line regimen
      (FOLFOX and cetuximab) in patients with RAS/v-Raf murine sarcoma viral oncogene homolog B
      (BRAF) wildtype, Microsatellite Instability (MSI) or icrosatellite Stability (MSS) MCRC with
      avelumab in terms of progression free survival rate after 12 months (acc. to Response
      Evaluation Criteria in Solid Tumors (RECIST) v1.1).

      The main secondary objective is to determine safety and tolerability, according to NCI Common
      Terminology Criteria for Adverse Events (CTCAE v4.03) and to the obtained data on vital
      signs, clinical parameters (oxygen saturation) and feasibility of the regimen. Further
      secondary objectives are to determine the efficacy of the experimental regimen in terms of
      objective response rate (acc. to RECIST v1.1 and irRECIST), and overall survival, to
      correlate clonal dynamics (RAS/EGFR subclones) with immune response signature to determine
      control of mutant subclones by the combination of anti-Epidermal growth factor receptor
      (EGFR) with anti-PD-L1and PD-L1 staining (and MSI status) with efficacy.
    

Trial Arms

NameTypeDescriptionInterventions
AVELUMABExperimental
  • Avelumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with histologically confirmed, previously untreated RAS and BRAF wildtype,
             MSI or MSS metastatic colorectal cancer (primary tumor may be present)

          2. Patients with at least one measurable lesion acc. to RECIST v1.1

          3. ECOG Performance status ≤ 1

          4. Life expectancy > 3 months

          5. Age ≥ 18 years.

          6. 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

          7. 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.

          8. Adequate renal function: serum creatinine ≤ 1.5 x ULN

          9. 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.

        11. 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

        Exclusion Criteria:

          1. 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)

          2. All subjects with known brain metastases, except those meeting the following criteria:

               1. Brain metastases that have been treated locally and are clinically stable for at
                  least 2 weeks prior to enrolment

               2. 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)

               3. Subjects must be either off steroids or on a stable or decreasing dose of <10mg
                  daily prednisone (or equivalent)

          3. Prior organ transplantation, including allogeneic stem-cell transplantation

          4. Significant acute or chronic infections including, among others:

               1. Known history of testing positive test for human immunodeficiency virus (HIV) or
                  known acquired immunodeficiency syndrome (AIDS)

               2. Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV
                  antibody tested positive)

          5. 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)

          6. Concomitant treatment with corticosteroids or other immunosuppressants, besides
             treatment of brain metastases as mentioned in criteria 2 or:

               1. 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

               2. Administration of steroids through a route known to result in a minimal systemic
                  exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable

          7. 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)

          8. Pregnancy or lactation

          9. 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.

        11. 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.

        12. 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 13. Any psychiatric condition that would
        prohibit the understanding or rendering of informed consent 14. Vaccination within 4 weeks
        of the first dose of avelumab and while on trial is prohibited except for administration of
        inactivated vaccines 15. Any approved anticancer therapy, including chemotherapy, hormonal
        therapy or radiotherapy, within 4 weeks prior to initiation of study treatment 16. Major
        surgical procedure within 28 days prior to treatment or anticipation of need for a major
        surgical procedure during the course of the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival Rate (PFS) @ 12 months
Time Frame:during 12 months of treatment
Safety Issue:
Description:PFS according to RECIST 1.1 at 12months of treatment

Secondary Outcome Measures

Measure:Safety
Time Frame:21 months
Safety Issue:
Description:Safety and tolerability (acc. to NCI CTC AE v4.03 and to the obtained data on vital signs, clinical parameters (oxygen saturation) and feasibility of the regimen)
Measure:Response Rate (RR)
Time Frame:4 years
Safety Issue:
Description:Response Rate (RR) according to RECIST v1.1 and modified RECIST (mRECIST)
Measure:Progression Free Survival (PFS)
Time Frame:4 years
Safety Issue:
Description:Progression Free Survival (PFS) according to RECIST v1.1 and mRECIST
Measure:Overall survival (OS)
Time Frame:4 years
Safety Issue:
Description:Overall survival (OS)
Measure:Translational research
Time Frame:48 months
Safety Issue:
Description:Translational research (correlation of clonal dynamics (RAS/EGFR subclones) with immune response signature to determine control of mutant subclones by the combination of anti-EGFR with anti-PD-L1, and PD-L1 (and MSI) status with efficacy

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AIO-Studien-gGmbH

Last Updated

October 9, 2017