Cancer
Conditions
Keywords
Radiosensitization, COX-2 inhibitor, Celecoxib, Head and Neck Cancer, Chemoradiation
Brief summary
This is a single-institution, open-label, non-randomized phase IB/II trial of celecoxib administered concurrently with carboplatin, paclitaxel, and radiation therapy in patients with locally advanced or recurrent squamous cell carcinoma of the head and neck.
Detailed description
Treatment for this protocol consists of radiotherapy, 70.2Gy, at 1.8Gy qd, Monday through Friday.Celecoxib 400mg bid is taken during radiotherapy, starting 1 week before radiotherapy. Carboplatin IV, AUC 2.0, weekly for weeks 1 through 7,Paclitaxel 45 mg/m2, weekly for weeks 1 through 7, and Celecoxib 400mg bid, continuing after therapy for two years or until disease progression.
Interventions
DRUGcelecoxib
400mg bid starting 1 week before radiotherapy and taken through radiotherapy.
DRUGCarboplatin
IV, AUC 2.0, weekly for weeks 1 through 7
DRUGPaclitaxel
IV 30 mg/m2, weekly for weeks 1 through 7
RADIATIONRadiation Therapy
70.2Gy, at 1.8Gy qd, Monday through Friday
Sponsors
Bristol-Myers Squibb
Pharmacia
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven primary squamous cell carcinoma arising in the oropharynx, oral cavity, hypopharynx, or larynx. Patients with recurrences after primary surgery (with no history of radiotherapy or chemotherapy) are also eligible. * The patient has stage III or IV disease, T3 or higher, or N2 or higher, nonmetastatic. Recurrent need not satisfy these staging requirements on restating, but patients must be nonmetastatic, and either be unresectable, medically inoperable, or refuse further surgery. * Performance status \< 2 (ECOG scale) with a life expectancy of \> 12 months. * Age \> 19 years. * The patient is medically fit to tolerate a course of definitive radiation therapy. * The patient has: * adequate hepatic function with bilirubin \< 1.5 x upper limit of normal (ULN), * transaminases (SGOT and SGPT) may be up to 2.5 x ULN if alkaline phosphatase is \< ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are \< ULN, * adequate renal function with serum creatinine \< 1.5 mg/dl (or estimated creatinine clearance of \> 50 mL/min), * normal serum calcium, * adequate hematologic function as: defined by an absolute neutrophil count \> 1500/ml, hematocrit \> 24 %, and platelet count \> 100,000/ml. Patients with hematocrit between 24 % and 30 % should undergo transfusion or treatment with epoetin, and may be enrolled. * The patient may have had a prior malignancy but must be disease-free for 5 years prior to study entry. A history of superficial non-melanoma skin cancer or in situ carcinoma of the cervix less than three years will be allowed. * The patient must agree to use effective contraception if procreative potential exists, and continue contraception for at least 3 months following completion of the study. * Patient must be informed of the investigational nature of the study and sign an informed consent form.
Exclusion criteria
* The patient has received radiation therapy previously to the head and neck. Previous radiotherapy for skin cancers of the head and neck are permitted if the fields do not overlap. * The patient has received prior chemotherapy for head and neck cancer. * The patient is pregnant or lactating. * Squamous cell carcinoma arising in the nasopharynx, sinuses, salivary glands, or the primary is unknown. * Non-squamous histologies (such as adenoid cystic or mucoepidermoid) * Peripheral neuropathy \> Grade 2. * Serious non-malignant disease (e.g. congestive heart failure, uncontrolled atrial fibrillation, active hepatitis, renal failure or renal transplant). * Scleroderma or active connective disorder (Lupus) * Allergy to celecoxib, sulfonamides, or other NSAIDS * Any underlying psychological condition that would prohibit the understanding and rendering of informed consent. * Major surgery \< 3 weeks prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity of Celecoxib With Concurrent Weekly Chemotherapy and Radiotherapy in the Treatment of Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck. | 2 years from radiation therapy | Particpants experiencing Acute Toxicities \> Grade 3 |
| Response as Evaluated by Recurrence of Diseases | 2 years from end of treatment (Radiation therapy) | Evaluate the response to concurrent celecoxib, carboplatin, paclitaxel, and radiotherapy in the treatment of locally advanced SSC of the head and neck. Response is determined by local control only, local and distant metastasis, distant metastasis only, second primary, and surgical salvage. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Celecoxib + Carboplatin/Paclitaxel+Radiation Therapy | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Celecoxib + Carboplatin/Paclitaxel+Radiation Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age Continuous | 53.83 years STANDARD_DEVIATION 8.06 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 30 |
| serious Total, serious adverse events | 12 / 30 |
Outcome results
Primary
Response as Evaluated by Recurrence of Diseases
Evaluate the response to concurrent celecoxib, carboplatin, paclitaxel, and radiotherapy in the treatment of locally advanced SSC of the head and neck. Response is determined by local control only, local and distant metastasis, distant metastasis only, second primary, and surgical salvage.
Time frame: 2 years from end of treatment (Radiation therapy)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Acute Toxicity | Response as Evaluated by Recurrence of Diseases | Surgical Salvage | 3 Participants |
| Acute Toxicity | Response as Evaluated by Recurrence of Diseases | Local Control Only | 6 Participants |
| Acute Toxicity | Response as Evaluated by Recurrence of Diseases | Local Control and Distant Metastasis | 2 Participants |
| Acute Toxicity | Response as Evaluated by Recurrence of Diseases | Distant Metastatsis Only | 1 Participants |
| Acute Toxicity | Response as Evaluated by Recurrence of Diseases | Secondary Primary - Site Unknown | 2 Participants |
Primary
Toxicity of Celecoxib With Concurrent Weekly Chemotherapy and Radiotherapy in the Treatment of Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck.
Particpants experiencing Acute Toxicities \> Grade 3
Time frame: 2 years from radiation therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Acute Toxicity | Toxicity of Celecoxib With Concurrent Weekly Chemotherapy and Radiotherapy in the Treatment of Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck. | Hematologic | 12 participants |
| Acute Toxicity | Toxicity of Celecoxib With Concurrent Weekly Chemotherapy and Radiotherapy in the Treatment of Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck. | Dermatitis | 7 participants |
| Acute Toxicity | Toxicity of Celecoxib With Concurrent Weekly Chemotherapy and Radiotherapy in the Treatment of Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck. | Mucositis/Dysphagia | 16 participants |