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Metastatic Colorectal CancerPhase 2AVETUXNCT03174405

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

A Phase 2 study testing Avelumab in people with Metastatic Colorectal Cancer, run by AIO-Studien-gGmbH at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Avelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteGermany
Study dates
17 Jul 2017to 16 Jul 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • 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

Who cannot join

  • 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:
  • 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
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  • 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.
  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg

Other trials in Germany

About this study

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.

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.

Read the 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.

Being tested
Avelumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    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)

Study groups in NCT03174405
Study groupRoleWhat they receive
AVELUMABExperimentalNot described
Receives: Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival Rate (PFS) @ 12 months

    PFS according to RECIST 1.1 at 12months of treatment

    Measured: during 12 months of treatment

Secondary outcomes (5)

  1. Safety

    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)

    Measured: 21 months

  2. Response Rate (RR)

    Response Rate (RR) according to RECIST v1.1 and modified RECIST (mRECIST)

    Measured: 4 years

  3. Progression Free Survival (PFS)

    Progression Free Survival (PFS) according to RECIST v1.1 and mRECIST

    Measured: 4 years

  4. Overall survival (OS)

    Overall survival (OS)

    Measured: 4 years

  5. Translational research

    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

    Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2017
  2. Study start17 Jul 2017
  3. Primary completion16 Jul 2020
  4. Study completion16 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03174405
Sponsor's protocol ID
AIO-KRK-0216
Other IDs
2016-004434-26, MS100070_0065, 2016
Acronym
AVETUX
Status last verified
Sep 2022
First submitted
31 May 2017
Last updated
29 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36605436

  • 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.

    PubMed 34315821

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avelumab in people with Metastatic Colorectal Cancer, run by AIO-Studien-gGmbH at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival Rate (PFS) @ 12 months (time frame: during 12 months of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03174405, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2022.

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