Head and Neck Cancer, Squamous Cell Cancer
Conditions
Brief summary
The purpose of this study is to investigate if zalutumumab in combination with Best Supportive Care (BSC) is superior to BSC in non-curable patients with head and neck cancer
Detailed description
This is an open parallel group trial. Patients will be randomized in a 2:1 manner to receive either treatment with zalutumumab in combination with Best Supportive Care (BSC) or BSC. Patients randomized to treatment with zalutumumab in combination with BSC will receive weekly infusions with zalutumumab starting with a loading dose (8mg/kg) followed by weekly maintenance doses until disease progression, intercurrent illness preventing further administration, unacceptable toxicity or patient decision. After Visit 2 the patient should be evaluated for presence of skin rash prior to each infusion to allow dose titration. Individual dose titration until the patient develops grade 2 skin rash will be applied. The maximum dose used in study will be 16 mg/kg.
Interventions
DRUGZalutumumab
Individual dose titration weekly i.v doses
OTHERControl
Best Supportive Care
Sponsors
Genmab
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and Females age ≥ 18 years 2. Confirmed diagnosis, initially or at relapse, of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, considered incurable with standard therapy 3. Failure to at least one course of standard platinum-based chemotherapy
Exclusion criteria
1. Three or more chemotherapy regimens other than platinum-based chemotherapy 2. Prior treatment with EGFr antibodies and/or EGFr small molecule inhibitors 3. Past or current malignancy other than SCCHN, except for certain other cancer diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization until death | A patient's overall survival was defined as the time from the date of randomization until the date of death from any cause, assessed up to 41 months. Overall survival was censored if the patient was lost to follow-up or refused to continue in the trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response | From date of randomization until the date of death from any cause, assessed up to 41 months. | Objective tumor response assessed according to Response Evaluation Criteria in Solid Tumours (RECIST v 1.0) J Natl Cancer Inst 2000;92:205-16 assessed by CT/MRI. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the longest diameter of target lesions; Overall Response (OR), CR+PR |
| Duration of Response | Time from complete or partial response until death, recurrence or progressive disease, assessed up to 41 months. | Duration of response defined as the time from the first date where measurement criteria for complete or partial response (whichever status is recorded first) are met until the first date that death, recurrence or progressive disease is objectively documented. |
| Progression Free Survival (PFS) | From randomization until disease progression or death, assessed up to 41 months. | PFS (defined as the time from randomization until disease progression or death). The progression events were defined by well-documented and verifiable imaging data. In case of censoring, the date of censoring had to be the last time point documenting the status of the patient. |
Countries
Belgium, Brazil, Canada, Estonia, France, Hungary, Lithuania, Poland, Russia, Serbia, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zalutumumab Zalutumumab in combination with Best Supportive Care | 191 |
| Control Best Supportive Care | 95 |
| Total | 286 |
Baseline characteristics
| Characteristic | Zalutumumab | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 18 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 161 Participants | 77 Participants | 238 Participants |
| Age Continuous | 57 years STANDARD_DEVIATION 9 | 57 years STANDARD_DEVIATION 9 | 57 years STANDARD_DEVIATION 9 |
| Region of Enrollment Belgium | 31 participants | 20 participants | 51 participants |
| Region of Enrollment Brazil | 7 participants | 4 participants | 11 participants |
| Region of Enrollment Canada | 10 participants | 8 participants | 18 participants |
| Region of Enrollment Estonia | 3 participants | 1 participants | 4 participants |
| Region of Enrollment France | 13 participants | 3 participants | 16 participants |
| Region of Enrollment Hungary | 37 participants | 20 participants | 57 participants |
| Region of Enrollment Lithuania | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Poland | 14 participants | 2 participants | 16 participants |
| Region of Enrollment Russian Federation | 42 participants | 22 participants | 64 participants |
| Region of Enrollment Serbia | 5 participants | 1 participants | 6 participants |
| Region of Enrollment Spain | 1 participants | 4 participants | 5 participants |
| Region of Enrollment Sweden | 4 participants | 0 participants | 4 participants |
| Region of Enrollment United Kingdom | 22 participants | 10 participants | 32 participants |
| Sex: Female, Male Female | 22 Participants | 12 Participants | 34 Participants |
| Sex: Female, Male Male | 169 Participants | 83 Participants | 252 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 188 / 189 | 92 / 94 |
| serious Total, serious adverse events | 180 / 189 | 87 / 94 |
Outcome results
Primary
Overall Survival
A patient's overall survival was defined as the time from the date of randomization until the date of death from any cause, assessed up to 41 months. Overall survival was censored if the patient was lost to follow-up or refused to continue in the trial.
Time frame: From randomization until death
Population: The full analysis set (FAS) was based on the intent-to-treat principle and thus comprised all randomized patients. The FAS was used for evaluation of all efficacy endpoints and was the primary analysis population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zalutumumab | Overall Survival | 6.7 months |
| Control | Overall Survival | 5.2 months |
Secondary
Duration of Response
Duration of response defined as the time from the first date where measurement criteria for complete or partial response (whichever status is recorded first) are met until the first date that death, recurrence or progressive disease is objectively documented.
Time frame: Time from complete or partial response until death, recurrence or progressive disease, assessed up to 41 months.
Population: The full analysis set (FAS) was based on the intent-to-treat principle and thus comprised all randomized patients. The FAS was used for evaluation of all efficacy endpoints and was the primary analysis population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zalutumumab | Duration of Response | 5.5 month |
| Control | Duration of Response | 7.4 month |
Secondary
Objective Tumor Response
Objective tumor response assessed according to Response Evaluation Criteria in Solid Tumours (RECIST v 1.0) J Natl Cancer Inst 2000;92:205-16 assessed by CT/MRI. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the longest diameter of target lesions; Overall Response (OR), CR+PR
Time frame: From date of randomization until the date of death from any cause, assessed up to 41 months.
Population: The full analysis set (FAS) was based on the intent-to-treat principle and thus comprised all randomized patients. The FAS was used for evaluation of all efficacy endpoints and was the primary analysis population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zalutumumab | Objective Tumor Response | Partial response | 10 participants |
| Zalutumumab | Objective Tumor Response | Progressive disease | 70 participants |
| Zalutumumab | Objective Tumor Response | Stable disease | 79 participants |
| Zalutumumab | Objective Tumor Response | Not evaluable | 30 participants |
| Zalutumumab | Objective Tumor Response | Complete response | 2 participants |
| Control | Objective Tumor Response | Not evaluable | 31 participants |
| Control | Objective Tumor Response | Complete response | 0 participants |
| Control | Objective Tumor Response | Partial response | 1 participants |
| Control | Objective Tumor Response | Stable disease | 25 participants |
| Control | Objective Tumor Response | Progressive disease | 38 participants |
Secondary
Progression Free Survival (PFS)
PFS (defined as the time from randomization until disease progression or death). The progression events were defined by well-documented and verifiable imaging data. In case of censoring, the date of censoring had to be the last time point documenting the status of the patient.
Time frame: From randomization until disease progression or death, assessed up to 41 months.
Population: The full analysis set (FAS) was based on the intent-to-treat principle and thus comprised all randomized patients. The FAS was used for evaluation of all efficacy endpoints and was the primary analysis population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zalutumumab | Progression Free Survival (PFS) | 9.9 weeks |
| Control | Progression Free Survival (PFS) | 8.4 weeks |