Bioimmunoradiotherapy (Cetuximab/RT/Avelumab)

NCT02938273 | Completed Phase 1

• 1 other identifier: N16BIR
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label phase IB trial with Bioimmunoradiotherapy, i.e. concurrent radiotherapy with intravenous administration of cetuximab and avelumab followed by avelumab maintenance therapy in patients with locally advanced head and neck cancer, unfit for cisplatin.

Conditions

Carcinoma, Squamous Cell of Head and Neck

Outcome Measures

Primary Outcomes (1)

• occurence of grade 3-5 toxicity in new combination

  according to CTC 4.03

  6 months after start of treatment

Secondary Outcomes (1)

• Overall Response Rate

  at week 10 and week 26 of treatment

Other Outcomes (1)

• differences in tumor microenvironment

  prior to treatment and at day 14

Study Arms (1)

Bioimmunoradiotherapy

EXPERIMENTAL

Concurrent Radiation therapy (i.e. 5 times a week, 7 weeks, total dose 70 Gy) with cetuximab (loading dose 400 mg/m2 i.v. day -7, 250 mg/m2 i.v weekly wk 1-7) and Avelumab10 mg/kg i.v. at day -7, 7, 21,35 + maintenance therapy i.e avelumab10 mg/kg i.v. every 2 weeks for 6 months (wk 8,10, 12, 14, 16, 18, 20, 22, 24, 26.

Drug: avelumab; Radiation: radiotherapy; Drug: cetuximab

Interventions

avelumab DRUG

Avelumab10 mg/kg i.v. at day -7, 7, 21,35 + maintenance therapy i.e avelumab10 mg/kg i.v. every 2 weeks for 6 months

Also known as: MSB0010718C

Bioimmunoradiotherapy

radiotherapy RADIATION

5 times a week, 7 weeks, total dose 70 Gy

Bioimmunoradiotherapy

cetuximab DRUG

loading dose 400 mg/m2 i.v. day -7, 250 mg/m2 i.v weekly wk 1-7

Also known as: erbitux

Bioimmunoradiotherapy

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥18 years of age on day of signing informed consent.
• WHO Performance Status 0,1 or 2
• Have histologically confirmed Locally Advanced (i.e. stage III or IV) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx.
• Unfit for concurrent chemoradiation with cisplatin, e.g. GFR \< 60 ml/min, cardiovascular co-morbidity, hearing loss or polyneuropathy or written refusal for treatment with chemotherapy
• Be willing to provide tissue for tumor microenvironment analysis from archival tumor material (i.e. formalin fixed, paraffin embedded (FFPE) tumor tissue block not older than 42 days before start of treatment) or newly obtained core or excisional biopsy, and willingness to provide a core or excisional biopsy at day 14 (±2 days) after start of treatment.
• Have at least one measurable lesion as defined by RECIST 1.1.
• Be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Demonstrate adequate organ function, i.e. adequate bone marrow function, including:
• Absolute Neutrophil Count (ANC) ≥1.5 x 109/L;
• Platelets ≥100 x 109/L;
• Hemoglobin ≥6 mmol/L. Adequate renal function, i.e. estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault (CG) equation (or local institutional standard method).
• Adequate liver function, including:
• Total serum bilirubin ≤1.5 x ULN;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).

You may not qualify if:

• \- Prior treatment with: Systemic therapy, radiotherapy or surgery directed at locally advanced SCCHN. Immunotherapy with IL-2, IFN-α, or anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Current or prior use of immunosuppressive medication within 7 days prior to registration, except the following:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma Global Initiative for Asthma 2011.
• Known prior or suspected hypersensitivity to study drugs or any component in their formulations.
• Diagnosis of any other malignancy within 5 years prior to start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g. surgery, radiation, or castration).
• 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)
• Prior organ transplantation, including allogeneic stem cell transplantation
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent, except the following:
• Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

Antoni van Leeuwenhoek

Amsterdam, 1066CX, Netherlands

Location

Related Publications (1)

• Elbers JBW, Al-Mamgani A, Tesseslaar MET, van den Brekel MWM, Lange CAH, van der Wal JE, Verheij M, Zuur CL, de Boer JP. Immuno-radiotherapy with cetuximab and avelumab for advanced stage head and neck squamous cell carcinoma: Results from a phase-I trial. Radiother Oncol. 2020 Jan;142:79-84. doi: 10.1016/j.radonc.2019.08.007. Epub 2019 Sep 26.

  PMID: 31563412 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

avelumab; Radiotherapy; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jan Paul de Boer, MD, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2016
• First Posted: October 19, 2016
• Study Start: February 1, 2017
• Primary Completion: June 26, 2019
• Study Completion: September 30, 2019
• Last Updated: December 11, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)