recurrent/metastatic head and neck squamous cell cancer MedDRA version: 20.0 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck
Conditions
Interventions
Trade Name: Bavencio
Product Name: Bavencio
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: avelumab
CAS
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically/cytologically confirmed recurrent/metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies. (NB: for the safety run-in, this criterion is replaced by "Histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma that is considered incurable by local therapies.") 2. Prior treatment with a platinum agent (either for recurrent/metastatic disease; or as part of radical intent multi-modality treatment if disease has recurred within 6 months). (NB: This cirterion is not applicable for the safety run-in). 3. No previous treatment with cetuximab for metastatic/recurrent disease 4. Age =18 years 5. WHO Performance Status 0 or 1 6. Measurable disease according to RECIST v1.1 7. Adequate bone marrow function 8. Adequate liver function 9. Adequate renal function 10. Adequate venous access for administration of treatment and collection blood samples for exploratory biological samples 11. Willing to have a new biopsy (NB: This criterion is not applicable for the safety run-in). 12. Life expectancy of >3 months 13. Women of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods from date of informed consent, which must be continued for 120 days after completion of trial treatment. 14. Able to give informed consent, indicating that the patient has been informed of and understands the experimental nature of the study, possible risks and benefits, trial procedures, and alternative options 15. Willing and able to comply with the protocol for the duration of the study, including the treatment plan, investigations required and follow up visits. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Patients with undifferentiated nasopharyngeal or sino-nasal cancers. 2. Disease suitable for treatment with curative intent. 3. Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent. 4. Treatment with any investigational agent within 4 weeks prior to the first dose of trial treatment. 5. Anti-cancer monoclonal antibody therapy within 4 weeks prior to randomisation 6. Chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to randomisation. 7. Persisting grade =2 toxicity related to prior therapy 8. Patients with concurrent or previous malignancy that could compromise assessment of the primary or secondary endpoints of the trial. 9. Women who are pregnant or breast feeding. 10. Grade 3 or 4 peripheral neuropathy. 11. Any serious and/or unstable pre-existing medical, psychiatric or other condition, 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. 12. Patients who are not able to give informed consent for any reason. 13. Active central nervous system (CNS) metastases and/or carcinomatous meningitis 14. Hepatitis infection at screening 15. Known history of testing positive for HIV or known acquired immunodeficiency syndrome. 16. Prior organ transplantation including allogenic stem-cell transplantation 17. Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis 18. Active infection requiring systemic therapy 19. Has received a live vaccine within 28 days prior to first dose of trial treatment 20. Has 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 (n.b. the use of physiologic doses of corticosteroids may be approved after consultation with UCL CTC) 21. Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. 22. Current use of immunosuppressive medication 23. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organising pneumonia (i.e. bronchiolitis obliterans, cryptogenic organising pneumonia), or evidence of active pneumonitis on screening chest CT scan. (History of radiation pneumonitis in the radiation field is permitted). 24. Significant cardiovascular disease 25. Known prior severe hypersensitivity to either investigational product or any component in their formulations, including known severe hypersensitivity reactions to monoclonal antibodies 26. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis. 27. Patients with a history of keratitis, ulcerative keratitis or severe dry eye.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Disease control rate (DCR) at 24 weeks after randomisation. Disease control is defined as the absence of objective progression according to iRECIST.; Main Objective: This trial is divided into two parts; a safety run-in and the phase II part of the trial. The objective of the safety run in is to make sure the combination of cetuximab and avelumab at the doses we have selected for the study are safe and tolerable. In phase II, the main question we want to answer is whether or not giving avelumab and cetuximab together is better than giving avelumab alone to treat patients with head and neck cancer that have had previous treatment with cisplatin and whose cancer has come back or spread to other parts of the body. We will compare the number of patients in each group whose cancer has not gotten any worse 6 months after joining the study. ;Secondary Objective: We will look at other measures of how effective the two treatments are, such as in how many patients does the cancer shrink, how long does it take before the cancer starts to grow, and how long do the patients live. We will also look at the side effects to see whether one treatment has more or less side effects than the other.;Timepoint(s) of evaluation of this end point: 24 weeks after randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Objective response (iCR or iPR) at 6 and 12 months using iRECIST 2) DC at 12 months using iRECIST 3) Duration of response using iRECIST 4) Best overall response (OR) using iRECIST 5) Time to progression (TTP) 6) Progression free survival (PFS) 7) Overall survival (OS) 8) Frequency and severity of adverse events 9) Treatment related dose delays or treatment discontinuation ; Timepoint(s) of evaluation of this end point: 1) 6 and 12 months after randomisation 2) 12 months after randomisation 3) From first response assessment showing iCR or iPR to assessment documenting iPD 4) From start of treatment to end of follow up 5) Randomisation to date of first progression 6) Randomisation to date last known alive 7) Randomisation to death from any cause | — |
Countries
United Kingdom
Contacts
Public ContactEACH Trial Coordinator
CR UK & UCL Cancer Trials Centre
Outcome results
None listed