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

This is an interventional treatment trial for Squamous Cell Carcinoma of the Skin Read More

Inclusion Criteria:

1. Patients must be 18 years of age or older.
2. Patients with histologically confirmed, unresectable cuSCC, stage I-IV (M0).
3. Patients must be capable of providing consent to enrolment and treatment.
4. Patients with a performance status of ECOG 0-2 will be eligible for enrolment
5. Measurable disease must be present according to RECIST 1.1 criteria.
6. 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.

7. 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.

8. 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.
9. 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.
10. 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.
11. The following adequate organ function laboratory values must be met:

Hematological:

• Absolute neutrophil count (ANC) >1.5 x109/L
• Platelet count >100 x109/L
• Hemoglobin >9 g/dL (may have been transfused)

Renal:

o Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)

Hepatic:

• Total serum bilirubin <1.5x ULN
• AST and ALT <2.5x ULN

Coagulation:

• International Normalized Ratio (INR) <1.5x ULN (unless patient is receiving anticoagulant therapy as long as prothrombin time (PT) or activated partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants)
• PTT <1.5x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)

Exclusion Criteria:

1. History of pneumonitis requiring treatment with steroids.
2. History of active interstitial lung disease.
3. 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.
4. 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.
5. Diagnosis of immunodeficiency.
6. 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).
7. Prior organ transplantation including allogeneic stem-cell transplantation.
8. Known history of human immunodeficiency virus (HIV).
9. 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).
10. 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.
11. Active infection requiring systemic therapy.
12. Vaccination within 4 weeks of the first dose of Avelumab and while on trials is prohibited except for administration of inactivated vaccines.
13. 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.
14. 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).
15. 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.
16. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 grade > 1); however, alopecia, sensory neuropathy ≤ grade 2, or other toxicities ≤ grade 2 not constituting a safety risk based on investigator's judgment are acceptable.