Head and Neck Cancer
Conditions
Keywords
Head and Neck Cancer, Erlotinib, RADPLAT
Brief summary
The purpose of this study is to determine the safety and effectiveness of treatment with Tarceva (Erlotinib) and RADPLAT (RADiation and intraarterial cisPLATin) for patients with Head and Neck cancer
Detailed description
Head and neck malignancies represent a group of epidermoid tumors that arise from the epithelial lining of the mouth, pharynx, and larynx. Three modalities of therapy have established roles in the treatment of carcinoma of the head and neck: chemotherapy, radiation therapy (XRT), and surgery. The choice of modality depends upon many factors such as the site and extent of the primary lesion, the likelihood of complete surgical resection, the presence of lymph node metastases, etc. Traditionally, smaller lesions (stage T1-T2) are effectively treated either, by surgical excision or irradiation whereas more advanced disease (stage III-IV) is treated with combined surgery and XRT. The subsequent morbidity related to extensive surgery is a major problem among survivors. Clearly, there is a need to develop therapeutic strategies for patients with advanced head and neck cancer with more effective approaches employing non-surgical modalities. Our hypothesis is that head and neck cancers are resistant to apoptosis from DNA damage induced by radiation and chemotherapy. This resistance is mediated by EGFR overexpression which results in downstream activation of cell survival signals, such as AKT, and may be overcome when Erlotinib (Tarceva) is co-administered with RADiation and cisPLATin (intraarterial chemotherapy).
Interventions
150 mg daily X 7 weeks
DRUGIntra-arterial Cisplatin (PLAT)
1 dose (150 mg/sq) per week X 4 weeks
RADIATIONRadiation Therapy (RAD)
5 days per week X 7 weeks
Sponsors
Genentech, Inc.
OSI Pharmaceuticals
Southern Illinois University
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
* Patients must have histologically or cytologically confirmed Stage III-IV disease comprised of T3 or T4 N0-2 lesions of the oral cavity, oropharynx, hypopharynx, and larynx. * No previous radiation therapy or chemotherapy. * No evidence of distant metastatic disease. * Age \> 18. * Karnofsky performance status of \> 60 (ECOG 2). * ANC \> 1000, platelets \> 100,000, calculated or 24-hour creatinine clearance \> 60. * Study-specific informed consent form. * Protocol treatment must begin \< 8 weeks of diagnostic biopsy. * Ability to understand and the willingness to sign a written informed consent document. * Patients with surgically cured secondary malignancy who have been disease free \> 5 years are eligible.
Exclusion criteria
* Radiologic evidence of bone destruction. * Previous or concurrent head and neck primaries. * Prior surgery to study site other than biopsy. * Patients receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because treatments and agents have the potential for teratogenic or abortifacient effects. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * History of a prior or concomitant malignancy (other than carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete and Partial Response Using RECIST Criteria | 17 weeks | Complete and Partial Response as defined by RECIST 1.0. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival Post Treatment | 22 months | Overall Survival with a minimum follow up of 1year. Relapse/Persistent Disease Rates |
Countries
United States
Participant flow
Recruitment details
Recruitment open between May 2006 and October 2009 at a small academic center outpatient otolaryngology/ oncology clinic.
Participants by arm
| Arm | Count |
|---|---|
| RADPLAT and Tarceva All patients will receive RADPLAT and Tarceva:
Drug: Erlotinib (Tarceva)
150 mg daily X 7 weeks
Other Names:
Tarceva
Drug: Intra-arterial Cisplatin (PLAT)
1 dose (150 mg/sq) per week X 4 weeks
Other Names:
Cisplatin
Radiation: Radiation Therapy (RAD)
5 days per week X 7 weeks
Erlotinib (Tarceva): 150 mg daily X 7 weeks
Intra-arterial Cisplatin (PLAT): 1 dose (150 mg/sq) per week X 4 weeks
Radiation Therapy (RAD): 5 days per week X 7 weeks | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | lack of insurance coverage for chemoRT | 1 |
| Overall Study | PT had medical condition preventing TX | 1 |
Baseline characteristics
| Characteristic | RADPLAT and Tarceva |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| N stage of Tumor at diagnosis N0 stage of tumor | 4 Participants |
| N stage of Tumor at diagnosis N1 stage of tumor | 4 Participants |
| N stage of Tumor at diagnosis N2 Stage of tumor | 13 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 19 Participants |
| T stage of Tumor at diagnosis T3 stage of tumor | 8 Participants |
| T stage of Tumor at diagnosis T4 stage of tumor | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 11 / 19 |
Outcome results
Primary
Number of Participants With Complete and Partial Response Using RECIST Criteria
Complete and Partial Response as defined by RECIST 1.0. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD
Time frame: 17 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RADPLAT and Tarceva | Number of Participants With Complete and Partial Response Using RECIST Criteria | Complete Response | 17 Participants |
| RADPLAT and Tarceva | Number of Participants With Complete and Partial Response Using RECIST Criteria | Partial Response | 2 Participants |
Secondary
Survival Post Treatment
Overall Survival with a minimum follow up of 1year. Relapse/Persistent Disease Rates
Time frame: 22 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RADPLAT and Tarceva | Survival Post Treatment | 12 participants |