Squamous Cell Cancers of the Head and Neck
Conditions
Brief summary
This is a single arm Phase II study for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with an immune checkpoint inhibitor. The primary objective is to evaluate the efficacy of the combination of cetuximab and afatinib.
Detailed description
This study will be a multicenter, single-arm, open-label Phase II trial. Patients with advanced squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with immune checkpoint inhibitor therapy or both, will be eligible for participation on the study. After a baseline evaluation and biopsy (where feasible), they will be treated with weekly/bi-weekly intravenous cetuximab and daily oral afatinib. Biopsy will be repeated where feasible after 4 weeks (window of +1 week) on therapy and again at disease progression or end of treatment. Treatment will continue until disease progression or development of Grade 3 or higher drug related toxicities that fail to resolve to Grade 2 despite appropriate supportive care.
Interventions
DRUGcetuximab
30-60 minutes after the recommended pre-medications, cetuximab will be administered intravenously at a dose of 400mg/m2 on cycle 1, day 1 of treatment (loading dose) and at a dose of 250mg/m2 every 7 days (+/- 1 day) thereafter. Alternatively, patients can be treated at a dose of 500mg/m2 every 14 days (+/- 2 days).
DRUGafatinib
Patients will take a single oral dose of afatinib each day at a dose of 30 mg. Afatinib dose will not be escalated beyond the 30 mg daily oral dose; dose reductions of afatinib can occur to manage treatment related adverse events.
Sponsors
Yale University
National Comprehensive Cancer Network
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed squamous cell carcinoma of the head and neck that is metastatic, recurrent or locally advanced and not treatable with curative intent. * Previous treatment with a platinum-based regimen or immune checkpoint inhibitor or both.2-week washout period prior to treatment start will be required. * Patients who have experienced progression of disease within 6 months following completion of a platinum-based chemoradiation in the definitive or adjuvant setting will be permitted. * Prior cetuximab permitted if it was given as part of multi-modality therapy for initial treatment of locally advanced disease. * Measurable disease based on RECIST v 1.1. Baseline measurements and evaluations must be obtained within 4 weeks of enrollment. Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy. * ECOG performance status ≤2 * Adequate organ function, defined as all of the following: * Hemoglobin ≥ 8 g/dl. * Absolute neutrophil count (ANC) ≥1000 / mm3. * Platelet count ≥75,000 / mm3. * Estimated creatinine clearance \> 45ml / min. * Total Bilirubin ≤ 1.5 times upper limit of (institutional/central) normal (Patients with Gilbert's syndrome total bilirubin must be ≤4 times institutional upper limit of normal). * Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ three times the upper limit of (institutional/central) normal (ULN) (if related to liver metastases ≤ five times ULN). * Ability to understand and the willingness to sign a written informed consent that is consistent with ICH-GCP guidelines. * Negative urine or serum pregnancy test for women of childbearing potential * A second eligibility review will always be provided by a Head and Neck Research Team associated for the New Haven Campus and a third review will be provided by the PI.
Exclusion criteria
* Prior erlotinib, gefitinib or lapatinib therapy or prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibody. Cetuximab is permitted if used for locally advanced disease, as long as no disease progression within 6 months. Cetuximab use is not permitted for recurrent/metastatic disease * Radiotherapy within 2 weeks prior to enrollment. Palliative radiation to target organs may be allowed up to 2 weeks prior to enrollment, as long as there are other target lesions that can be monitored for response to study treatment. * Known hypersensitivity to afatinib or its excipients * Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control prior to study entry, for the duration of study participation and for at least 4 weeks after treatment has ended. * Women who are pregnant, nursing, or who plan to become pregnant while in the trial. * Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug. * Concomitant malignancies at other sites that are being actively treated with systemic therapy * Requiring treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation. * Clinically significant interstitial lung disease. * Known history of untreated viral hepatitis or HIV. * Patients with parenchymal brain metastases are not eligible, unless they have completed local therapy * Leptomeningeal carcinomatosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Shrinkage | Disease progression or end of treatment (up to 2 years) | Objective Response Rate (Complete Response + Partial Response), defined by tumor shrinkage (mm), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RECIST v1.1 Response Categories are as follows: Complete Response (CR) - all pathological lymph nodes must be \< 10 mm in short axis; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) - The cancer has neither clearly improved nor worsened. Progressive Disease (PD) - at least a 20% increase in the sum of diameters of target lesions AND an absolute increase of ≥ 5 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival in Months | 1 year follow-up | We will use Kaplan-Meier survival analysis to estimate the median PFS in the cohort. Data are presented by P16 status. The outcome measure title was updated to present the data in months, as analyzed, instead of weeks as originally registered. |
| Overall Survival in Months | 1 year follow-up | Measured by a monthly phone calls. We will use Kaplan-Meier survival analysis to estimate the median and OS in the cohort. |
| Duration of Response in Weeks | Up to 6 years | Presented is the time from treatment onset until best response. |
| Toxicity Assessed With National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Up to 2.5 years | Presented are a count of those that experienced at least 1 adverse event. Adverse event details are presented in the Adverse Events module. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAarti Bhatia, MD, MPH
Yale University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| P16 Status Negative | 29 Participants |
| P16 Status Positive | 21 Participants |
| Prior Lines of Treatment Anti-PD-1 | 37 Participants |
| Prior Lines of Treatment Platinum | 49 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 43 Participants |
| Region of Enrollment United States | 50 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 44 / 50 |
| other Total, other adverse events | 49 / 50 |
| serious Total, serious adverse events | 20 / 50 |
Outcome results
None listed