R-M Head and Neck Cancer MedDRA version: 20.0 Level: PT Classification code 10034813 Term: Pharyngeal cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10055104 Term: Pharyngeal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: BAVENCIO
Product Name: BAVENCIO
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
Current Sponsor code: Avelumab
Concentration unit: mg/kg milligram(
Sponsors
G.O.N.O. - GRUPPO ONCOLOGICO DEL NORD OVEST
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for the translational study. 2. Be = 18 years of age on day of signing informed consent. 3. ECOG Performance Status 0-2. 4. Have histologically or cytologically-confirmed recurrent or metastatic (disseminated) head and neck squamous cell carcinoma 5. Have a disease progression after treatment with at least one line of therapy including at least Cisplatin, Fluorouracil and Cetuximab for recurrent (disease not amenable to curative treatment)/metastatic disease. 6. Measurable disease by RECIST criteria. 7. At least one metastatic site suitable for irradiation 8. Life expectancy > 3 months. 9. Adequate bone marrow function: neutrophils = 1.5 x 109/L, platelets = 100 x 109/L, hemoglobin =9 g/dL. 10. Adequate liver function: AST and ALT levels = 2.5 × ULN; bilirubin = 1.5 x ULN. 11. Adequate renal function: creatinine clearance = 30 mL/min (Cockroft-Gault). 12. Fertil men must be using adequate contraceptive measures throughout the study period if their partner are women of childbearing potential. 13. If of childbearing potential, women must use effective contraceptive method (Pearl Index =65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: 1. History of malignant disease (with the exception of non-melanoma skin tumours and/or in situ cervical cancer) in the preceding five years. 2. Brain metastases. 3. Autoimmune disorders. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. 4. Allergic disorders. 5. Cyclophosphamide treatment contraindications: a. Cystitis. b. Urinary Obstruction. c. Inadequate bone marrow function: WBC 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable. 15. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; 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. Avelumab treatment contraindications: a. Hypersensitivity to the active ingredient or to any excipient. b. Inadequate bone marrow function: WBC <2900 mm3 and/or HCT <30% and/or platelets count <90000 mm3. c. Uncontrolled serous effusions (pleural, pericardic or peritoneal) d. Blood Pressure <60 mmHg. e. Pregnancy or breast feeding. f. Active infections. Known history of testing positive for HIV or known acquired immunodeficiency syndrome. g. Brain metastases. h. 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. 17. Participation to other concomitant experimental study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: a.Assessment of the safety of the combination of avelumab, mCTX and non ablative radiotherapy (phase I). b.Assessment of activity of avelumab, mCTX and non ablative radiotherapy in a population of heavily pre-treated RM-HNSCC patients (phase II). ;Secondary Objective: c.Assessment of the safety of the combination of avelumab, mCTX and non ablative radiotherapy. d.Description of progression free survival (PFS) and overall survival (OS) e.Exploratory description of Health-related Quality of Life ;Primary end point(s): The primary endpoint of the phase I trial is the absence of unacceptable toxicity. Assessment of the safety profile of the association of avelumab and metronomic cyclophosphamide will be graded using the common toxicity criteria and adverse events (NCI CTC-AE v 4.0).;Timepoint(s) of evaluation of this end point: Every 4 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Assessment of the safety profile of the association of avelumab and metronomic cyclophosphamide will be graded using the common toxicity criteria and adverse events (NCI CTC-AE v 4.0). • Progression free survival is defined as the time from study treatment initiation to the first occurrence of disease progression or death of any cause, whichever occurs first; Overall survival is defined as the time from treatment initiation to death for any cause. • Quality of Life will be assessed using the EORTC QLQ -30 and EORTC QLQ – H&N35 ;Timepoint(s) of evaluation of this end point: Every 4 weeks | — |
Countries
Italy
Contacts
Public ContactUFFICIO SPERIMENTAZIONI CLINICHE
A. O. S. CROCE E CARLE DI CUNEO
Outcome results
None listed