Head and Neck Cancer
Conditions
Keywords
Head and Neck Cancer, GEMCITABINE, PEMETREXED, ALTIMA, epidermoid/squamous cell, carcinoma, pharynx, larynx, paranasal sinus, head/neck squamous cell carcinoma
Brief summary
The purpose of this study is to determine if the combination of 2 chemotherapy drugs called pemetrexed and gemcitabine might be effective treatment for head and neck squamous cell cancer. The researchers want to find out what effects, good and/or bad, that this treatment has on head and neck cancer.
Detailed description
Pemetrexed (500 mg/m2) and gemcitabine (1250 mg/m2) will be given together on Days 1 and 15 of a 28 day cycle in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Patients will not have received more than 2 prior chemotherapy regimens in the recurrent/metastatic disease setting. Vitamin B12 and folate supplementation will be administered per standard guidelines for pemetrexed chemotherapy. The primary endpoint is the objective radiologic response rate. Radiologic imaging of evaluable disease will take place after every 2 cycles. Patients may remain on study until progression of disease or unacceptable toxicity.
Interventions
DRUGPemetrexed plus Gemcitabine
Patients will receive pemetrexed (500 mg/m2 IV infusion over approximately 10 minutes) followed immediately by gemcitabine (1250 mg/m2 IV infusion given over approximately 30 minutes) on day 1 and day 15 of a 28-day cycle. Vitamin supplementation will be as follows: Vitamin B12: 1000 µg IM injection no less than 1 week prior to the first dose of pemetrexed, and continuing approximately every 9 weeks until 3 weeks after the last dose of pemetrexed. Folic acid: The preferred oral daily dose of folic acid is 350 to 1000 µg. Daily folate supplementation begins no less than 1 week prior to the first dose of pemetrexed and continues until 3 weeks after the last dose of pemetrexed. For rash prophylaxis, dexamethasone (4 mg po twice per day) should be taken on the day before, the day of, and the day after each dose of pemetrexed unless clinical contraindications exist.
Sponsors
Memorial Sloan Kettering Cancer Center
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 microscopically confirmed epidermoid/squamous cell carcinoma (HNSCC) of the oral cavity, pharynx, larynx, paranasal sinus, or head/neck squamous cell carcinoma unknown primary. * Patients must have recurrent or metastatic disease which is not amenable to curative-intent therapy with surgery or radiation. * No more than 2 prior cytotoxic therapies in the recurrent or metastatic disease setting are permitted. * Patients must be at least 18 years of age. * Karnofsky Performance status must be ≥ 70%. * Disease must be measurable by RECIST criteria. * At least 4 weeks must have elapsed from previous radiation therapy. Patient must have recovered from the acute toxic effects of treatment prior to study enrollment. * Prior radiation therapy to ≤ 25% of bone marrow is allowed. Prior radiation to the whole pelvis and/or brain is not allowed. * Adequate organ function * Patients of childbearing potential must have a negative test for pregnancy at time of enrollment based on a urine or serum pregnancy test. Patients must agree to use a reliable method of birth control during and for 3 months following the last dose of study drug. * Patient must reside in geographic proximity to MSKCC for adequate follow-up during treatment, per investigator discretion. * Patients must sign an informed consent document.
Exclusion criteria
* Previous exposure to pemetrexed (Alimta) or gemcitabine (Gemzar). * Pregnancy or breast-feeding. * Serious concomitant systemic disorders (for example, active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study. * History of any brain metastases. * Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone. * Patients will be excluded if they will be unable to hold use of nonsteroidal antiinflammatory agents (NSAIDS) with short elimination half lives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Objective Response | 2 years | To determine the objective radiologic response rate of pemetrexed and gemcitabine in patients with recurrent or metastatic Head and Neck Squamouse Cell Carcinoma. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | 2 years | To determine the median overall survival for patients with recurrent or metastatic Head and Neck Squamous Cell Carcinoma treated with pemetrexed and gemcitabine. |
Countries
United States
Participant flow
Recruitment details
Protocol Open to Accrual 09/08/1998 Protocol Closed to Accrual 07/22/2008 Primary Completion Date 07/13/2010 Recruitment Location is the medical clinic.
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed Plus Gemcitabine Patients will receive pemetrexed (500 mg/m2 IV infusion over approximately 10 minutes) followed immediately by gemcitabine (1250 mg/m2 IV infusion given over approximately 30 minutes) on day 1 and day 15 of a 28-day cycle. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Pemetrexed Plus Gemcitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 52.5 years STANDARD_DEVIATION 43.13351365 |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 25 |
| serious Total, serious adverse events | 12 / 25 |
Outcome results
Primary
Overall Objective Response
To determine the objective radiologic response rate of pemetrexed and gemcitabine in patients with recurrent or metastatic Head and Neck Squamouse Cell Carcinoma. 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: 2 years
Population: All assessable patients as indicated in the protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed Plus Gemcitabine | Overall Objective Response | Partial Response | 4 participants |
| Pemetrexed Plus Gemcitabine | Overall Objective Response | Stable Disease | 18 participants |
| Pemetrexed Plus Gemcitabine | Overall Objective Response | Progression of Disease | 2 participants |
| Pemetrexed Plus Gemcitabine | Overall Objective Response | Response not available | 1 participants |
Secondary
Median Overall Survival
To determine the median overall survival for patients with recurrent or metastatic Head and Neck Squamous Cell Carcinoma treated with pemetrexed and gemcitabine.
Time frame: 2 years
Population: There were 25 assessable patients as described in the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed Plus Gemcitabine | Median Overall Survival | 8.8 months |