Head and Neck Cancer
Conditions
Keywords
Cetuximab, Erbitux, locally, advanced, head, neck, cancer, neoplasms, squamous, carcinoma, lymphoepithelioma
Brief summary
The main purpose of this study is to explore and compare the efficacy of Cetuximab (ERBITUX®) added to two concurrent chemoradiotherapy platforms of different intensity in locally advanced head and neck cancer.
Interventions
DRUGCetuximab
250mg/m2(day 1, weekly x 10);
DRUG5-FU
600 mg/m2/day; days 0-5 (120 h total) every other week x 5
DRUGHydroxyurea
500 mg PO BID, days 0-5 every other week x 5
RADIATIONTwice-daily radiation
150 cGy per fraction, days 1-5, every other week x 5 (total duration 10 weeks)
DRUGCisplatin
100 mg/m2, week 1 and 4 on day 1 (or 2)
RADIATIONAccelerated fraction radiotherapy with concomitant boost
72 Gy/42 F/6 W (3-D or IMRT based). Total duration 7 weeks.
Sponsors
Bristol-Myers Squibb
University of Chicago
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
* Age 18 or older * Stage III and IV head and neck cancer * Patients with squamous cell carcinoma of unknown primary and suspected origin in the head and neck area * No prior chemotherapy or radiotherapy * Prior surgical therapy of incisional or excisional biopsy and organ-sparing procedures only * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 * Normal organ and marrow function
Exclusion criteria
* Unequivocal demonstration of metastatic disease * Known severe hypersensitivity to drugs used in the study * Treatment with a non-approved or investigational drug within 30 days before Day 1 * Incomplete healing from previous surgery * Pregnancy or breast feeding * Uncontrolled intercurrent illness including * Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF * Acute hepatitis or known HIV * Severe baseline neurologic deficits * Prior therapy which specifically and directly targets the EGFR pathway * Prior severe infusion reaction to a monoclonal antibody
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 1 years | Kaplan-Meier estimate of PFS at 1 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 2 years | Time from randomization until death from any cause. Kaplan-Meier estimate of OS at 2 years. |
| Objective Response Rate to Induction | Post-Induction (8 weeks) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Objective Response Rate to CRT | From date of chemoradiotherapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 weeks | Response to CRT was assessed by determining whether there was evidence of residual disease in the primary site via radiographic and clinical examination. |
| Residual Lymph Node Disease | Up to 10 weeks | Response to CRT was also assessed by determining if there was evidence of residual lymph node disease by neck dissection, if warranted by the presence of any radiographically large (\>1.5 cm) or focally abnormal lymph node. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A: Cetuximab+FHX Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
Cetuximab: Cetuximab - Arm A:250mg/m2(day 1, weekly x 10); Cetuximab - Arm B:250mg/m2(day 1, weekly x 7) | 57 |
| B: Cetuximab + PX Cetuximab \[250 mg/m2 (day 1, weekly x7)\] + PX (Cisplatin \[100mg/m2 (week 1 & 4 on day 1 (or 2))\], Accelerated fraction radiotherapy with concomitant boost \[AFX-CB (72 Gy/42 F/6 W) (3-D or IMRT based)\]). Total duration: 7 weeks.
Cetuximab: Cetuximab - Arm A:250mg/m2(day 1, weekly x 10); Cetuximab - Arm B:250mg/m2(day 1, weekly x 7) | 53 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | B: Cetuximab + PX | Total | A: Cetuximab+FHX |
|---|---|---|---|
| Age, Continuous | 55.6 years | 55.8 years | 56.1 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 22 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 39 Participants | 83 Participants | 44 Participants |
| Sex: Female, Male Female | 9 Participants | 17 Participants | 8 Participants |
| Sex: Female, Male Male | 44 Participants | 93 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 57 | 9 / 53 |
| other Total, other adverse events | 57 / 57 | 53 / 53 |
| serious Total, serious adverse events | 7 / 57 | 14 / 53 |
Outcome results
Primary
Progression Free Survival (PFS)
Kaplan-Meier estimate of PFS at 1 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 1 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A: Cetuximab+FHX | Progression Free Survival (PFS) | 87.7 Probability (%) |
| B: Cetuximab + PX | Progression Free Survival (PFS) | 92.5 Probability (%) |
p-value: 0.1225Log Rank
Primary
Progression Free Survival (PFS)
Time from randomization until disease progression or death from any cause. Kaplan-Meier estimate of PFS at 2 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A: Cetuximab+FHX | Progression Free Survival (PFS) | 82.5 Probability (%) |
| B: Cetuximab + PX | Progression Free Survival (PFS) | 84.9 Probability (%) |
Secondary
Objective Response Rate to CRT
Response to CRT was assessed by determining whether there was evidence of residual disease in the primary site via radiographic and clinical examination.
Time frame: From date of chemoradiotherapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A: Cetuximab+FHX | Objective Response Rate to CRT | 3 Participants |
| B: Cetuximab + PX | Objective Response Rate to CRT | 4 Participants |
Secondary
Objective Response Rate to Induction
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Post-Induction (8 weeks)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A: Cetuximab+FHX | Objective Response Rate to Induction | Partial Response (PR) | 47 Participants |
| A: Cetuximab+FHX | Objective Response Rate to Induction | Complete Response (CR) | 7 Participants |
| A: Cetuximab+FHX | Objective Response Rate to Induction | Progressive Disease (PD) | 0 Participants |
| A: Cetuximab+FHX | Objective Response Rate to Induction | Stable Disease (SD) | 3 Participants |
| B: Cetuximab + PX | Objective Response Rate to Induction | Progressive Disease (PD) | 1 Participants |
| B: Cetuximab + PX | Objective Response Rate to Induction | Complete Response (CR) | 4 Participants |
| B: Cetuximab + PX | Objective Response Rate to Induction | Stable Disease (SD) | 7 Participants |
| B: Cetuximab + PX | Objective Response Rate to Induction | Partial Response (PR) | 41 Participants |
Secondary
Overall Survival (OS)
Time from randomization until death from any cause. Kaplan-Meier estimate of OS at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A: Cetuximab+FHX | Overall Survival (OS) | 91.2 Probability (%) |
| B: Cetuximab + PX | Overall Survival (OS) | 94.3 Probability (%) |
Secondary
Residual Lymph Node Disease
Response to CRT was also assessed by determining if there was evidence of residual lymph node disease by neck dissection, if warranted by the presence of any radiographically large (\>1.5 cm) or focally abnormal lymph node.
Time frame: Up to 10 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A: Cetuximab+FHX | Residual Lymph Node Disease | 2 Participants |
| B: Cetuximab + PX | Residual Lymph Node Disease | 6 Participants |