Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)
- Conditions
- Squamous Cell Carcinoma of the Head and Neck
- Interventions
- Other: Chemoradiation
- Registration Number
- NCT02952586
- Lead Sponsor
- Pfizer
- Brief Summary
This is a phase 3 randomized, placebo controlled study to evaluate the safety and anti-tumor activity of Avelumab in combination with standard of care chemoradiation (SoC CRT) versus SoC CRT alone in front-line treatment of patients with locally advanced head and neck cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 697
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + SOC CRT Chemoradiation * Placebo IV matching avelumab: Days 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; Q2W for 12 months during the Maintenance Phase * Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase * IMRT 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase Avelumab + SOC Chemoradiation Therapy Avelumab * Avelumab 10 mg/kg IV: Day 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; and Q2W for 12 months during the Maintenance Phase * Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase * Intensity Modulated Radiation Therapy (IMRT) 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months) PFS was defined as the time (in months) from the date of randomization to the first documentation of objective progressive disease (PD) per modified RECIST v1.1 as assessed by Investigator or death (due to any cause), whichever occurred first. Analysis was performed using Kaplan Meier method. PD refers to any of following: 1) Locoregional PD confirmed by pathology to verify radiographic changes represent true tumor progression and not radiation effects or non-malignant contrast enhancement. 2) Locoregional clinically detectable progression confirmed by pathology. 3) Surgical removal (salvage) of primary tumor with tumor present on final pathology. 4) Salvage neck dissection greater than (\>) 20 weeks after completion of CRT with tumor present on final pathology. 5) Metastatic PD. PFS data was censored on date of last adequate tumor assessment for participants with no PFS event.
- Secondary Outcome Measures
Name Time Method Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site From randomization until PD or death (up to 37 months) pCR was defined as the absence of histologically identifiable residual cancer in any resected specimen. The pCR rate at primary site was estimated by dividing the number of participants with pCR recorded at any visit from randomization until PD per modified RECIST v1.1 or death due to any cause by the number of participants randomized who had salvage surgery at the primary site.
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated worse health status. In VAS participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status.
Overall Survival (OS) From randomization to the date of death or censored date, whichever occurred first (up to 37 months) Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan Meier method.
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Baseline up to 15 months Grade 1 and 3 ranges are: Anemia:Hb:\<LLN-10.0,\<8.0 g/dL;LC decreased (dec):\<LLN-800/mm\^3,500-200/mm\^3;LC increased (inc):grade 3:\>20,000/mm\^3:NC dec:\<LLN-1500/mm\^3;\<1000-500/mm\^3;PC dec:\<LLN-75,000/mm\^3;\<50,000-25,000/mm\^3;WBC dec:\<LLN-3000/mm\^3;\<2000-1000/mm\^3;ALT inc:\>ULN-3.0\*ULN;\>5.0-20.0\*ULN;ALP \& GGT inc:\>ULN-2.5\*ULN;\>5.0-20.0\*ULN;AST inc:\>ULN-3.0\*ULN;\>5.0-20.0\*ULN;BB inc:\>ULN-1.5\*ULN;\>3.0-10.0\*ULN;CH high:\>ULN-300 mg/dL;\>400-500 mg/dL;CPK inc:\>ULN-2.5\*ULN;\>5\*ULN-10\*ULN;Hypercalcemia:\>ULN-11.5;\>12.5-13.5mg/dL;Hyperglycemia:\>ULN-160; \>250-500mg/dL;Hyperkalemia:\>ULN-5.5;\>6.0-7.0mmol/L;Hypermagnesemia:\>ULN-3.0;\>3.0-8.0 mg/dL;Hypernatremia:\>ULN-150; \>155-160 mmol/L;Hypertriglyceridemia;150-300;\>500-1000 mg/dL;Hypoalbuminemia:\<LLN-3;\<2g/dL;Hypocalcemia:\<LLN-8.0;\<8.0-7.0mg/dL;Hypokalemia:\<LLN-3.0;\<3.0-2.5mmol/L;Hypomagnesemia;\<LLN-1.2;\<0.9-0.7 mg/dL;Hyponatremia:\<LLN-130;\<130-120mmol/L; Hypophosphatemia:\<LLN-2.5;\<2.0-1.0mg/dL;lipase \& serum amylase inc:\>ULN-1.5\*ULN;\>2.0-5.0\*ULN.
Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator From the date of randomization to the date of the first documentation of locoregional recurrence or death, whichever occurred first (up to 37 months) Locoregional failure was defined as the time from the date of randomization to the date of the first documentation of locoregional recurrence or death due to any cause per modified RECIST v1.1 as assessed by Investigator, whichever occurred first. Analysis was performed using Kaplan Meier method.
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug) Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured in sitting position were reported.
Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator From randomization until disease progression or death, whichever occurred first (up to 37 months) Objective response (OR) was defined as a complete response (CR) or partial response (PR) per RECIST v1.1 recorded from randomization until disease progression per modified RECIST v1.1 or death due to any cause. A participant was considered to have achieved an OR if the participant had a CR or PR which did not need to be confirmed at a subsequent assessment. CR for target disease: complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis less than \[\<\] 10 millimeter \[mm\]). CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (\<10 mm short axis) . PR: Greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target measurable lesions. The ORR was estimated by dividing the number of participants with OR (CR or PR) by the number of participants randomized.
Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator From the date of randomization to the date of the first documentation of distant metastatic or death (up to 37 months) Time to distant metastatic failure or distant metastasis (DM) was defined as the time from the date of randomization to the date of the first documentation of distant metastatic or death due to any cause, whichever occurred first. Distant metastatic disease was defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes. Analysis was performed using Kaplan Meier method.
Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator From the first documentation of objective tumor response to the first documentation of PD or death or censored date, whichever occurred first (up to 37 months) DOR:time from first documentation of objective tumor response (CR/PR) to first documentation of PD/death due to any cause, whichever occurred first.PR:\>=30% decrease under baseline of sum of diameters of all target measurable lesions. CR for target disease:complete disappearance of all target lesions with exception of nodal disease.CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. PD is any of following:1)Locoregional PD confirmed by pathology to verify radiographic changes denote true tumor progression and not radiation effects or non-malignant contrast enhancement.2)Locoregional clinically detectable progression confirmed by pathology.3)Surgical removal of primary tumor with tumor present on final pathology.4)Salvage neck dissection \>20 weeks after completion of CRT with tumor present on final pathology.5)Metastatic PD. DOR data was censored on date of last adequate tumor assessment for participants with no overall response.
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) Baseline (prior to first dose) PD-L1 biomarker expression in tumor tissue as assessed by IHC in the form of positive immune cells and tumor staining cells.
Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells Baseline (prior to first dose) Description: CD8+ cells are the type of T-lymphocytes. Mean percentage of total tumor area occupied by CD8+ Cells has been reported. Area was measured in millimeter square (mm\^2).
Maximum Plasma Concentration (Cmax) of Avelumab Pre-dose and end of infusion on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1 and 2 (each cycle 28 days) Maximum observed plasma concentration (Cmax) of Avelumab is reported.
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). AUClast (dn) was calculated by dividing AUClast by the exact dose of cisplastin (in mg) administered to a participant.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Baseline up to 44 months Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. TEAE was defined as event with onset dates occurring during the on-treatment period.
Percentage of Participants With Positive and Negative Pathology of Neck Dissection From randomization until PD as per investigator assessment (up to 37 months) Percentage of participants with positive and negative pathology of neck dissection were reported. Positive pathology included live tumor cells present or 10% or greater vital tumor tissues. Negative pathology included no live tumor cells present, complete tumor regression, no evidence of vital tumor tissues, less than 10% vital tumor tissue, or not consistent with disease under study.
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase Time to reach maximum observed plasma concentration (Tmax) of total and free Cisplatin.
Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status Day 1 of lead-in phase and on Days 8 and 25 of CRT phase Change From Baseline in Vital Sign - Pulse Rate Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug) Change from baseline in pulse rate in sitting position in beats per minute was reported.
Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) The NCCN FHNSI-22 questionnaire measured disease symptoms, treatment side effects and overall quality of life in participants with head and neck cancer. The questionnaire contained 22 items with 5-point Likert scales ranging from 0 to 4 as follows: 'not at all = 0', a little bit = 1, somewhat = 2, quite a bit = 3 and very much = 4. Total score ranged from 0 to 88 where, higher scores represented better symptomatology, quality of life or functioning.
Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of total and free Cisplastin (in mg) administered to a participant.
Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status pre-dose on Day 1 up to 30 Days after the end of treatment ADA never-positive was defined as no positive ADA results at any time point; ADA-negative participants (titer less than\< cut point) and ADA ever-positive was defined as at least one positive ADA result at any time point; ADA-positive participants (titer greater than or equal to cut point)
Predose Plasma Concentration (Ctrough) of Avelumab Pre-dose on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1, 2, 5, 8, 11 (each cycle 28 days) Ctrough refers to plasma concentration of Avelumab observed just before treatment administration.
Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase Maximum observed plasma concentration (Cmax) of total and free Cisplatin is reported.
Trial Locations
- Locations (288)
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Tower Hematology Oncology Medical Group
🇺🇸Beverly Hills, California, United States
UCSD Radiation Oncology South Bay, Cancer Treatment Centers
🇺🇸Chula Vista, California, United States
City of Hope Corona
🇺🇸Corona, California, United States
Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc.
🇺🇸Riverside, California, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
🇺🇸Duarte, California, United States
UC San Diego Medical Center- La Jolla (Thornton Hospital)
🇺🇸La Jolla, California, United States
Scroll for more (278 remaining)Highlands Oncology Group🇺🇸Springdale, Arkansas, United States