Clinical Trials List
Protocol NumberB9991016
NCT Number(ClinicalTrials.gov Identfier)NCT02952586
2016-12-26 - 2021-04-08
Phase III
Terminated7
ICD-10C44.42
Squamous cell carcinoma of skin of scalp and neck
A RANDOMIZED DOUBLE-BLIND PHASE 3 STUDY OF AVELUMAB IN COMBINATION WITH STANDARD OF CARE CHEMORADIOTHERAPY (CISPLATIN PLUS DEFINITIVE RADIATION THERAPY) VERSUS STANDARD OF CARE CHEMORADIOTHERAPY IN THE FRONT-LINE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
-
Trial Applicant
Syneos Health
-
Sponsor
Pfizer, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 劉奕廷 無
- 吳沅樺 無
- 楊明維 無
- Shang-Yin Wu 無
- 薛尉廷 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 黃品逸 無
- 戴世光 無
- Sheng-Yu Chen 無
- Muh-Hwa Yang 無
- Yuan-Hung Wu 無
- Chia-Fan Chang 無
- Ling-Wei Wang 無
- 朱本元 無
- 陳盛裕 未分科
- 胡育文 無
- Tsung-Lun Lee 無
The Actual Total Number of Participants Enrolled
17 Stop recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- RUEY-LONG HONG 無
- 陳婉瑜 無
- 廖斌志 無
- 王駿瑋 無
- HUAI-CHENG HUANG 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Squamous Cell Carcinoma of the Head and Neck
Objectives
Primary Objective
To demonstrate that treatment with avelumab in combination with SOC CRT is superior to
SOC CRT alone in prolonging PFS in front-line patients with high risk (as defined in
Inclusion Criterion 2 [Section 4.1]), locally advanced SCCHN who are candidates for
definitive CRT with cisplatin.
Test Drug
MSB0010718C 20mg/ml Solution for Infusion
Active Ingredient
Avelumab (MSB0010718C)
Dosage Form
Solution for Infusion
Dosage
200
Endpoints
Primary Endpoint
PFS per modified RECIST v1.1 (see Appendix 3 for specific modifications, including
pathologic confirmation) by investigator assessment.
Secondary Endpoints
OS.
Antitumor activity: Pathologic complete response in any resected specimens, neck
dissection.
Antitumor activity: Locoregional failure, objective response, distant metastatic
failure, and duration of response, per modified RECIST v1.1 by investigator
assessment.
Safety: Adverse events and laboratory abnormalities as graded by National Cancer
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03;
vital signs (blood pressure, pulse rate).
Pharmacokinetics:
Cmax and Ctrough for avelumab;
Area under the concentration-time curve extrapolated to infinity (AUCinf),
Cmax, clearance (CL), time to maximum plasma concentration (Tmax),
elimination half-life (t1/2), and volume of distribution (Vz) for cisplatin (total
and free), as data permit.
Immunogenicity: ADA (neutralizing antibody) against avelumab.
Patient-Reported Outcomes: Disease-related symptoms and Health-Related Quality
of Life as measured by the National Cancer Comprehensive Network (NCCN) Head
and Neck Symptom Index-22 items (FHNSI-22), and the EuroQoL Group 5-
Dimension 5- Level Self-Report Questionnaire (EQ-5D-5L).
Biomarkers: Tumor tissue biomarkers including but not limited to, PD-L1 expression
and tumor-infiltrating CD8+ T-lymphocytes.
Exploratory Endpoints
Biomarkers: Peripheral blood and/or tumor tissue biomarkers consisting of the levels
of cells, DNA, RNA, or proteins that may be related to antitumor immune response
and/or disease progression on avelumab or in combination with CRT.
PET scan evaluation and pathological evaluation of neck dissection.
Patient-Reported Outcomes: Outcome measures for symptomatic AE as measured by
the items selected from the PRO-CTCAE item library.
PFS per modified RECIST v1.1 (see Appendix 3 for specific modifications, including
pathologic confirmation) by investigator assessment.
Secondary Endpoints
OS.
Antitumor activity: Pathologic complete response in any resected specimens, neck
dissection.
Antitumor activity: Locoregional failure, objective response, distant metastatic
failure, and duration of response, per modified RECIST v1.1 by investigator
assessment.
Safety: Adverse events and laboratory abnormalities as graded by National Cancer
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03;
vital signs (blood pressure, pulse rate).
Pharmacokinetics:
Cmax and Ctrough for avelumab;
Area under the concentration-time curve extrapolated to infinity (AUCinf),
Cmax, clearance (CL), time to maximum plasma concentration (Tmax),
elimination half-life (t1/2), and volume of distribution (Vz) for cisplatin (total
and free), as data permit.
Immunogenicity: ADA (neutralizing antibody) against avelumab.
Patient-Reported Outcomes: Disease-related symptoms and Health-Related Quality
of Life as measured by the National Cancer Comprehensive Network (NCCN) Head
and Neck Symptom Index-22 items (FHNSI-22), and the EuroQoL Group 5-
Dimension 5- Level Self-Report Questionnaire (EQ-5D-5L).
Biomarkers: Tumor tissue biomarkers including but not limited to, PD-L1 expression
and tumor-infiltrating CD8+ T-lymphocytes.
Exploratory Endpoints
Biomarkers: Peripheral blood and/or tumor tissue biomarkers consisting of the levels
of cells, DNA, RNA, or proteins that may be related to antitumor immune response
and/or disease progression on avelumab or in combination with CRT.
PET scan evaluation and pathological evaluation of neck dissection.
Patient-Reported Outcomes: Outcome measures for symptomatic AE as measured by
the items selected from the PRO-CTCAE item library.
Inclution Criteria
Inclusion Criteria
Patient eligibility should be reviewed and documented by an appropriate member of the
investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the
study:
1. Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx,
hypopharynx, or larynx with tissue available.
2. High-risk disease as defined by:
HPV-negative disease, Stage III, IVa, IVb per tumor/nodes/metastasis (TNM)
guidelines for head and neck sites (American Joint Committee on Cancer [AJCC]
7
th Edition);
42 or
Non-oropharyngeal HPV-positive disease, Stage III, IVa, IVb per TNM
guidelines for head and neck sites (AJCC 7th Edition);
42 or
HPV-positive oropharyngeal disease T4, N2c, or N3 per TNM guidelines for head
and neck sites (AJCC 7th Edition);
42
where HPV status will be determined per institutional standard using p16 immunohistochemistry (IHC).
3. No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative
intent.
4. Available tumor samples for submission or willing to undergo further tumor biopsies:
Availability of a formalin-fixed paraffin-embedded (FFPE) tumor tissue block
from primary tumor or nodal biopsy. If an FFPE tissue block cannot be provided,
15 unstained slides (10 minimum) will be acceptable.
5. Age ≥18 years (≥20 years in Japan).
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
(Appendix 2).
7. Adequate bone marrow function, including:
Absolute Neutrophil Count (ANC) ≥1,800/µL or ≥1.8 x 109
/L.
Platelets ≥100,000/µL or ≥100 x 109
/L.
Hemoglobin ≥9 g/dL (may have been transfused).
8. Adequate renal function, including:
Estimated creatinine clearance ≥50 mL/min as calculated using the
Cockcroft-Gault (CG) equation.
9. Adequate liver function, including:
Total serum bilirubin ≤1.5 x upper limit of normal (ULN).
Aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x ULN.
10. Pregnancy test (for patients of childbearing potential) negative at screening.
11. Male patients able to father children and female patients of childbearing potential and at
risk for pregnancy must agree to use two highly effective methods of contraception
throughout the study and for at least 6 months after the last dose of cisplatin and 60 days
after the last dose of avelumab/placebo (whichever is later).
Female patients who are not of childbearing potential (ie, meet at least one of the
following criteria):
a. Have undergone a documented hysterectomy and/or bilateral oophorectomy; or
b. Have medically confirmed ovarian failure; or
Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or
physiological cause and have a serum follicle-stimulating hormone (FSH) level
confirming the post-menopausal state.
12. Evidence of a signed and dated informed consent document indicating that the patient (or
a legally acceptable representative, as allowed by local guideline/practice) has been
informed of all pertinent aspects of the study.
13. Patients who are willing and able to comply with scheduled visits, treatment plans,
laboratory tests, and other study procedures.
Patient eligibility should be reviewed and documented by an appropriate member of the
investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the
study:
1. Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx,
hypopharynx, or larynx with tissue available.
2. High-risk disease as defined by:
HPV-negative disease, Stage III, IVa, IVb per tumor/nodes/metastasis (TNM)
guidelines for head and neck sites (American Joint Committee on Cancer [AJCC]
7
th Edition);
42 or
Non-oropharyngeal HPV-positive disease, Stage III, IVa, IVb per TNM
guidelines for head and neck sites (AJCC 7th Edition);
42 or
HPV-positive oropharyngeal disease T4, N2c, or N3 per TNM guidelines for head
and neck sites (AJCC 7th Edition);
42
where HPV status will be determined per institutional standard using p16 immunohistochemistry (IHC).
3. No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative
intent.
4. Available tumor samples for submission or willing to undergo further tumor biopsies:
Availability of a formalin-fixed paraffin-embedded (FFPE) tumor tissue block
from primary tumor or nodal biopsy. If an FFPE tissue block cannot be provided,
15 unstained slides (10 minimum) will be acceptable.
5. Age ≥18 years (≥20 years in Japan).
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
(Appendix 2).
7. Adequate bone marrow function, including:
Absolute Neutrophil Count (ANC) ≥1,800/µL or ≥1.8 x 109
/L.
Platelets ≥100,000/µL or ≥100 x 109
/L.
Hemoglobin ≥9 g/dL (may have been transfused).
8. Adequate renal function, including:
Estimated creatinine clearance ≥50 mL/min as calculated using the
Cockcroft-Gault (CG) equation.
9. Adequate liver function, including:
Total serum bilirubin ≤1.5 x upper limit of normal (ULN).
Aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x ULN.
10. Pregnancy test (for patients of childbearing potential) negative at screening.
11. Male patients able to father children and female patients of childbearing potential and at
risk for pregnancy must agree to use two highly effective methods of contraception
throughout the study and for at least 6 months after the last dose of cisplatin and 60 days
after the last dose of avelumab/placebo (whichever is later).
Female patients who are not of childbearing potential (ie, meet at least one of the
following criteria):
a. Have undergone a documented hysterectomy and/or bilateral oophorectomy; or
b. Have medically confirmed ovarian failure; or
Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or
physiological cause and have a serum follicle-stimulating hormone (FSH) level
confirming the post-menopausal state.
12. Evidence of a signed and dated informed consent document indicating that the patient (or
a legally acceptable representative, as allowed by local guideline/practice) has been
informed of all pertinent aspects of the study.
13. Patients who are willing and able to comply with scheduled visits, treatment plans,
laboratory tests, and other study procedures.
Exclusion Criteria
Exclusion Criteria
Patients with any of the following characteristics/conditions will not be included in the study:
1. Prior immunotherapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically
targeting T cell co-stimulation or immune checkpoint pathways.
2. Major surgery 4 weeks prior to randomization.
3. Diagnosis of any other malignancy within 5 years prior to randomization, except for
superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer
(Gleason score ≤6) either curatively treated or deemed to not require treatment, ductal in
situ carcinoma of the breast that has completed curative treatment, adequately treated
basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or bladder.
4. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease
not requiring immunosuppressive treatment are eligible.
5. Any of the following in the 6 months prior to randomization: myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive
heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic
pulmonary embolism.
6. Active infection requiring systemic therapy.
8. Use of immunosuppressive medication at time of randomization, except the following:
a. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular
injection);
b. Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or
equivalent;
c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
9. Prior organ transplantation including allogenic stem-cell transplantation.
10. Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or
acquired immunodeficiency syndrome (AIDS) related illness.
11. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV
surface antigen or HCV RNA [ribonucleic acid] if anti-HCV antibody screening test
positive).
12. Vaccination within 4 weeks prior to randomization except for administration of
inactivated vaccines.
13. Current use of or anticipated need for treatment with other anti-cancer drugs.
14. Pregnant female patients, breastfeeding female patients, and male patients able to father
children and female patients of childbearing potential who are unwilling or unable to use
2 highly effective methods of contraception as outlined in the protocol for the duration of
the study and for at least 6 months after the last dose of cisplatin and 60 days after the last
dose of avelumab/placebo (whichever is later).
15. Other severe acute or chronic medical conditions including: colitis, inflammatory bowel
disease, pneumonitis, pulmonary fibrosis, or psychiatric condition including recent
(within the past year) or active suicidal ideation or behavior; or laboratory abnormality
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. Patients who are investigational site staff members directly involved in the conduct of the
study and their family members, site staff members otherwise supervised by the
investigator, or patients who are Pfizer employees directly involved in the conduct of the
study.
17. Participation in other interventional studies involving investigational drug(s) within 4
weeks prior to randomization.
7. Known prior severe hypersensitivity to investigational products or any component in the
formulations, including known severe hypersensitivity reactions to mAbs, cisplatin, or
platinum-related compounds (NCI CTCAE v4.03 Grade ≥ 3).
Patients with any of the following characteristics/conditions will not be included in the study:
1. Prior immunotherapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically
targeting T cell co-stimulation or immune checkpoint pathways.
2. Major surgery 4 weeks prior to randomization.
3. Diagnosis of any other malignancy within 5 years prior to randomization, except for
superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer
(Gleason score ≤6) either curatively treated or deemed to not require treatment, ductal in
situ carcinoma of the breast that has completed curative treatment, adequately treated
basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or bladder.
4. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease
not requiring immunosuppressive treatment are eligible.
5. Any of the following in the 6 months prior to randomization: myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive
heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic
pulmonary embolism.
6. Active infection requiring systemic therapy.
8. Use of immunosuppressive medication at time of randomization, except the following:
a. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular
injection);
b. Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or
equivalent;
c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
9. Prior organ transplantation including allogenic stem-cell transplantation.
10. Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or
acquired immunodeficiency syndrome (AIDS) related illness.
11. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV
surface antigen or HCV RNA [ribonucleic acid] if anti-HCV antibody screening test
positive).
12. Vaccination within 4 weeks prior to randomization except for administration of
inactivated vaccines.
13. Current use of or anticipated need for treatment with other anti-cancer drugs.
14. Pregnant female patients, breastfeeding female patients, and male patients able to father
children and female patients of childbearing potential who are unwilling or unable to use
2 highly effective methods of contraception as outlined in the protocol for the duration of
the study and for at least 6 months after the last dose of cisplatin and 60 days after the last
dose of avelumab/placebo (whichever is later).
15. Other severe acute or chronic medical conditions including: colitis, inflammatory bowel
disease, pneumonitis, pulmonary fibrosis, or psychiatric condition including recent
(within the past year) or active suicidal ideation or behavior; or laboratory abnormality
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. Patients who are investigational site staff members directly involved in the conduct of the
study and their family members, site staff members otherwise supervised by the
investigator, or patients who are Pfizer employees directly involved in the conduct of the
study.
17. Participation in other interventional studies involving investigational drug(s) within 4
weeks prior to randomization.
7. Known prior severe hypersensitivity to investigational products or any component in the
formulations, including known severe hypersensitivity reactions to mAbs, cisplatin, or
platinum-related compounds (NCI CTCAE v4.03 Grade ≥ 3).
The Estimated Number of Participants
-
Taiwan
87 participants
-
Global
640 participants
