The UNSCARRed Study: UNresctable Squamous Cell Carcinoma Treated With Avelumab and Radical Radiotherapy

NCT03737721 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: UNSCARRed: IIT-0004
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out what effects the combination of radiation therapy and Avelumab have on you and your cancer. The effectiveness of this treatment as well as what side effects occur will both be studied. Squamous cell carcinoma of the skin is the most commonly diagnosed cancer. Risk factors for the development of squamous cell cancer include ultraviolet (sun) exposure, as well as increasing age. In the majority of instances, a minor surgical procedure is curative. Less commonly, squamous cell carcinoma cannot be removed surgically, due to the location and/or extent of the cancer, or due to patient-specific factors which would make surgery unsafe (for instance, the presence of unrelated medical illnesses such as heart disease or stroke). When squamous cell carcinoma cannot be removed surgically, radiation therapy may serve as an effective alternative treatment. Squamous cell carcinomas are typically very sensitive to radiation, and in some instances radiation therapy may also cure a person of their cancer. While some people may be cured by radiation therapy, not all people are. This study is investigating the combination of radiation therapy and immune therapy. When given together, more patients may be cured of their cancer. Immune therapy is effective for the treatment of squamous cell carcinoma. In clinical trials, more than half of patients benefit from immune therapy. Immune therapy is not chemotherapy. Instead, immune therapy involves the infusion of antibodies which target a person's own immune system. Immune therapy "re-activates" a person's own immune system against their cancer. The treatment offered within this clinical trial includes daily radiation treatments as well as immunotherapy treatments administered once every two weeks. The immunotherapy in use is a drug called Avelumab, which is an antibody that helps your body's immune system fight cancer. Health Canada, the regulatory body that oversees the use of natural health products, drugs and devices in Canada, has not approved the sale or use of this product to treat this kind of cancer, although they have allowed its use in this study

Conditions

Squamous Cell Carcinoma of the Skin

Outcome Measures

Primary Outcomes (1)

• Objective response rate (assessing change in tumour response before treatment vs after)

  Associated with combination Avelumab/radiation therapy (defined as the proportion of patients achieving either a partial response or a complete response as best-overall response per RECIST criteria 1.1)

  Primary analysis to occur approximately 36 weeks after LPFV. Baseline staging at screening,repeated at 90 day fup and confirmatory scan

Secondary Outcomes (3)

• Progression-free survival

  PFS will be based on the disease assessment or date of death provided by the investigator. The analysis of PFS will be scheduled to occur approximately 90 days following completion of the 24 month follow-up period for the final patient enrolled to study

• Clinical and pathological response rate

  The analysis of clinical and pathological response will be conducted within 90 days of enrollment of the last patient to study

• Safety analysis: CTCAE v.4.03

  Delegated study personnel will assess the patients for adverse events at baseline through to study completion per protocol (Baseline, cycles 1-5 (each cycle is 14 days), and in follow up at 30 days, 90 days and every 12 weeks up to 2 years).

Other Outcomes (4)

• Utility of tumoral PD-L1 expression as a predictive and prognostic biomarker

  Tumor biopsies will be obtained prior to treatment (baseline), following Avelumab monotherapy (post-cycle 1 treatment) and following completion of Avelumab concurrent with radiation therapy (end of cycle 4). Each cycle is 14 days.

• Quantification/characterization of tumor-infiltrating lymphocytes/PBMCs

  Blood samples will be obtained prior to treatment (baseline), after Avelumab monotherapy (post-cycle 1 treatment) following completion of Avelumab concurrent with radiation therapy (end of cycle 4). Each cycle is 14 days.

• Characterization of tumoral MHC-I/II expression/ Analysis of MHC immunopeptidomes

  Tumor biopsies will be obtained prior to treatment (baseline), following Avelumab monotherapy (post-cycle 1 treatment) and following completion of Avelumab concurrent with radiation therapy. Each cycle is 14 days.

Study Arms (1)

Avelumab and Radical radiotherapy

EXPERIMENTAL

Single-arm combining Avelumab with radical radiotherapy.

Combination Product: Avelumab and Radical radiotherapy

Interventions

Avelumab and Radical radiotherapy COMBINATION_PRODUCT

A single-arm, interventional study combining Avelumab with radical radiotherapy. Avelumab will be delivered on a 14-day cycle, with the first cycle administered 14 days in advance of the radiation therapy start date; 63-66 Gy radiation will be delivered over 30 daily fractions concurrent with an additional 4 cycles of Avelumab

Avelumab and Radical radiotherapy

Eligibility Criteria

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

You may qualify if:

• Patients must be 18 years of age or older.
• Patients with histologically confirmed, unresectable cuSCC, stage I-IV (M0).
• Patients must be capable of providing consent to enrolment and treatment.
• Patients with a performance status of ECOG 0-2 will be eligible for enrolment
• Measurable disease must be present according to RECIST 1.1 criteria.
• Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level \> 40 mIU/mL to confirm menopause.
• Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 30 days after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
• Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
• Female patients who are breast-feeding should discontinue nursing prior to the first dose of study treatment and until 30 days after the last dose of study drug.
• Male patients should agree to not donate sperm during the study and for a period of at least 30 days after last dose of study drug.
• Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
• The following adequate organ function laboratory values must be met:
• Hematological:
• Absolute neutrophil count (ANC) \>1.5 x109/L
• Platelet count \>100 x109/L

You may not qualify if:

• History of pneumonitis requiring treatment with steroids.
• History of active interstitial lung disease.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• History of another malignancy or a concurrent malignancy; Exceptions include patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ.
• Diagnosis of immunodeficiency.
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Prior organ transplantation including allogeneic stem-cell transplantation.
• Known history of human immunodeficiency virus (HIV).
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV ribonucleic acid (RNA) if anti-HCV antibody screening test positive).
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Active infection requiring systemic therapy.
• Vaccination within 4 weeks of the first dose of Avelumab and while on trials is prohibited except for administration of inactivated vaccines.
• Patient will not be eligible if the patient is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective independent ethics committee (IEC) approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE v4.03 Grade ≥ 3).
• Other severe acute or chronic medical conditions including inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead
• EMD Serono: collaborator
• Alberta Cancer Foundation: collaborator

Study Sites (2)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G1Z2, Canada

Location

MeSH Terms

Interventions

avelumab

Study Officials

• John Walker, Walker

  Alberta Health Services - Cross Cancer Institute

  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

Model Details: This study has been designed as an open-label, non-randomized, single-arm phase II study to investigate the feasibility and efficacy of Avelumab in combination with radiation therapy in patients with unresectable cuSCC.

Study Record Dates

• First Submitted: October 26, 2018
• First Posted: November 9, 2018
• Study Start: April 12, 2019
• Primary Completion: July 15, 2024
• Study Completion: July 15, 2024
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

CA (2)