Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Mouth and Tooth Diseases

Musculoskeletal Diseases

Rare Diseases

Recurrence

Head and Neck Neoplasms

Laryngeal Diseases

Paranasal Sinus Neoplasms

Laryngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Nose Neoplasms

Nose Diseases

Paranasal Sinus Diseases

Laryngeal Cancer

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Antineoplastic Agents

Amino Acids

Mitogens

Celecoxib

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Tyrosine

In this phase I/II study, patients will be treated with daily erlotinib 150 mg and twice-daily celecoxib 200 to 600 mg for 14 days. Re-irradiation with IMRT will start on day 15 and will continue for 5.5 to 6.5 weeks along with erlotinib and celecoxib. After completion of radiation, patients will be given the option of continuing on erlotinib for 2 years or until unacceptable toxicity or disease progression

erlotinib + celecoxib

Johnny Kao, M.D.

There is no optimal treatment for patients with recurrent head and neck cancer after previous radiation. Chemotherapy alone is not curative and patients survive an average of only 6 to 10 months. Surgery is not always possible and often cannot remove every cancerous cell. On the other hand, reirradiation with chemotherapy cures approximately 25 to 30% of patients but has significant toxicity with as many as 15 to 20% suffering from life-threatening or fatal complications. Therefore, less toxic and more effective reirradiation regimens are urgently needed. There are extensive data from animal studies and preliminary human studies showing that blocking epidermal growth factor receptor (EGFR) and COX-2 enhances radiation effect and is more effective than either treatment alone. Erlotinib is a FDA approved oral inhibitor of EGFR and celecoxib is a FDA approved COX-2 inhibitor. Both have been well studied in humans and appear to have less severe toxicity than conventional chemotherapeutic agents.

Despite advances in the treatment of head and neck cancer, locoregional recurrences are the predominant site of treatment failure and are frequently the cause of death. Second primary tumors in the head and neck occur in up to 30% of patients at 10 years of follow-up after eradication of the original tumor due to field cancerization. The standard approach to patients with recurrent but non-metastatic disease has been surgical salvage alone. Unfortunately, this strategy is feasible in only a select group of patients and 5 year survival rates have ranged from 15-40%.

Most patients with previously irradiated unresectable recurrent or metastatic head and neck cancer are treated with chemotherapy alone. This approach has offered limited palliation with response rates of 10-40%, median survival of 5 to 10 months. While this may be an acceptable option for patients with clearly incurable widespread metastatic disease, it may not be the best approach for those patients with potentially curable locoregional disease.

While geographic misses and second primary tumors occur, the majority of patients have radioresistant tumors. Therefore, reirradiation alone is unlikely to be effective. High dose reirradiation with concomitant chemotherapy represents a more aggressive approach resulted in encouraging 3-year survival rates of 15 to 35%. This approach represents a potentially curative option for patients with unresectable or partially resected disease arising in a previously irradiated volume. However, the high rates of acute and late toxicity with this approach have limited widespread application of this approach.

Extensive preclinical and clinical data suggest that both epidermal growth factor receptor (EGFR) antagonists and cyclooxygenase-2 (COX-2) inhibitors enhance the effectiveness of ionizing radiation. In locally advanced head and neck cancer, a recent phase III trial concurrent anti-EGFR monoclonal antibody and radiation demonstrated improved local control, disease free survival and overall survival compared to radiation alone without the increased mucosal toxicity associated with concurrent chemotherapy. COX-2 inhibition and anti-EGFR therapy demonstrates activity against recurrent/metastatic head and neck cancer in a recent phase I study. Head and neck cancer represents an ideal site to study biologic markers of tumor response because of the accessibility of tumors for biopsy. Therefore, we propose the combination of Erlotinib and Celecoxib with radiation in a cohort of previously irradiation patients with head and neck cancer.

Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer

Phase I/II Dose Escalation Trial of Induction and Concomitant Erlotinib and Celecoxib With Radiation Therapy for Treatment of Poor Prognosis Head and Neck Cancer, Including Reirradiation

Number of participants with acute and late toxicity

Response to Concurrent Erlotinib, Celecoxib, and Reirradiation according to Response Evaluation Criteria in Solid Tumors - 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 Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

Patients with locoregional and/or distant progression

At a median follow-up of 11 months, the 1 year locoregional control, progression-free survival, and overall survival rates.

Johnny Kao

Assistant Professor

erlotinib + celecoxib: In this phase I/II study, patients will be treated with daily erlotinib 150 mg and twice-daily celecoxib 200 to 600 mg for 14 days. Re-irradiation with IMRT will start on day 15 and will continue for 5.5 to 6.5 weeks along with erlotinib and celecoxib. After completion of radiation, patients will be given the option of continuing on erlotinib for 2 years or until unacceptable toxicity or disease progression

Erlotinib + Celecoxib

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

The Eastern Cooperative Oncology Group (ECOG) 0 - Fully active, able to carry on all pre-disease performance without restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature 2- Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours

ECOG Performance Status

None to minimal

20-40

Unknown

Tobacco use, pack-years

Primary recurrence

Second or later recurrence

Second primary cancer

Recurrent vs secondary primary

Squamous cell carcinoma

Adenoid cystic

Histology

Sinonasal

Ear/facial skin

Oropharynx

Oral cavity

Hypopharynx

Larynx

Primary Site

Tx-T3

T4 --\> Tumor of any size with direct extension to chest wall or skin Tx - T3 --\> any tumor not classified as T4

Primary tumor classification

N0 - tumor cells absent from regional lymph nodes N1 - regional lymph node metastasis present; (at some sites; tumor spread to closest or small number of regional lymph nodes)

Lymph node status

15 subjects consented, one withdrew before receiving study treatment and was excluded from analysis

Dr. Johnny Kao

Dose Level 1: Patients administered 150mg Erlotinib daily and 200mg Celecoxib twice daily

Celecoxib 200mg

Dose Level 2: Patients administered 150mg Erlotinib daily and 400mg Celecoxib twice daily

Celecoxib 400mg

Dose Level 3: Patients administered 150mg Erlotinib daily and 600mg Celecoxib twice daily

Celecoxib 600mg

Erlotinib and celecoxib were administered orally

Toxicity

Complete Response(CR)

Pathologic partial response (pPR)

Progressive disease (PD)

No evidence of disease (NED)

Clinical Response

free of disease

isolated locoregional progression

isolated distant progression

both locoregional and distant progression

no evidence of disease, died of comorbid illness

Locoregional Progression

locoregional control

progress-free survival

overall survival rates

long term toxicity

Locoregional Control, Progression-free Survival, Overall Survival and Late Toxicity

Overall Study

Antisickling Agents

Docetaxel

Fluorouracil

Cisplatin

Hydroxyurea

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (75 mg/m2, day 1), cisplatin (75 mg/m2, day 1), and 5-fluorouracil (750 mg/m2/day, days 1-5). Total duration of 6 weeks.

Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.

Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.

75 mg/m2 on day 1 (induction phase); 25 mg/m2 on day 1 (chemoradiotherapy phase)

docetaxel

cisplatin

Each cycle: 500 mg PO q 12 hours x 6 days (11 doses)

hydroxyurea

750 mg/m2/day on days 1-5 (induction phase); 600 mg/m2/day, day 0-4 (chemoradiotherapy phase)

fluorouracil

chemotherapy

radiotherapy

Everett Vokes, M.D.

The combined use of chemotherapeutic drugs with radiation has proven to be effective in improving overall survival and local control among patients with locally advanced head and neck cancer. Induction chemotherapy given before receiving local treatment has been shown to reduce the rate of distant failure. Many drugs have been found to prevent tumor cells from growing or dividing, although it has yet to be determined which agent, or specific combination of agents, is most effective in treating head and neck cancer. Docetaxel is a drug which has been reported to show promising activity in Phase II head and neck cancer studies. Therefore, the purpose of this trial is to compare the effectiveness of induction chemotherapy followed by chemoradiotherapy versus the same chemoradiotherapy alone in patients with locally advanced head and neck cancer.

TRIAL DESIGN:

Phase III trial of induction therapy with docetaxel followed by chemoradiotherapy versus chemoradiotherapy alone in patients with nodal stage N2 or N3 head and neck cancer

OBJECTIVES:

Primary

* To determine the effect on overall survival when induction chemotherapy is administered prior to chemoradiotherapy in patients with N2 or N3 disease.

Secondary

* To determine the effect of induction chemotherapy when administered prior to chemoradiotherapy on distant failure-free survival, failure pattern, progression free survival and quality of life.

TREATMENT PLAN:

* After eligibility is confirmed, patients will be randomized to one of two treatment arms:

Arm A - Induction + chemoradiotherapy

Arm B - Chemoradiotherapy alone

* Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (day 1), cisplatin (day 1), and 5-fluorouracil (days 1-5). Total duration of 6 weeks.
* Chemoradiotherapy: Five 14-day cycles of docetaxel (day 1), 5-fluorouracil (day 0-4), and hydroxyurea (days 0-4) with twice daily radiation (days 1-5). Total duration of 10 weeks.
* All patients will undergo surgical evaluation after chemoradiation for possible neck dissection.
* Upon completion of treatment, patients will be monitored every three months during the first year, every six months during the second and third years, and annually thereafter, up to seven years.
* Patients will be followed for Quality of Life (QOL) during the course of treatment, as well as annually thereafter, up to five years.

PROJECTED ACCRUAL:

* An expected sample size of 400 patients will be enrolled for this study (200 per treatment arm).

Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer (DeCIDE)

A Phase III Randomized Trial of Docetaxel Based Induction Chemotherapy in Patients With N2/N3 Locally Advanced Head and Neck Cancer

DFFS rates over 6 years. DFFS is time from randomization to distant recurrence or death from any cause

Recurrence-free survival rates over 6 years. Recurrence-free survival is time from randomization to local, regional, or distant recurrence or death from any cause

Percentage of patients with local/regional recurrence

Percentage of patients with distant recurrence

FACT Hand-and-neck subscale(b) (0-40 point scale with negative numbers indicating worsening of function)

Performance Status Score (0-100 point scale with negative numbers indicating worsening of function)

McMaster RT Questionnaire (4-28 point scale with negative numbers indicating worsening of function)

University of Chicago

Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (75 mg/m2, day 1), cisplatin (75 mg/m2, day 1), and 5-fluorouracil (750 mg/m2/day, days 1-5). Total duration of 6 weeks.

Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.

docetaxel: 75 mg/m2 on day 1 (induction phase); 25 mg/m2 on day 1 (chemoradiotherapy phase)

cisplatin: 75 mg/m2 on day 1

hydroxyurea: Each cycle: 500 mg PO q 12 hours x 6 days (11 doses)

fluorouracil: 750 mg/m2/day on days 1-5 (induction phase); 600 mg/m2/day, day 0-4 (chemoradiotherapy phase)

chemotherapy: See protocol for details

radiotherapy: See protocol for details

Induction Plus Chemoradiotherapy

Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.

docetaxel: 75 mg/m2 on day 1 (induction phase); 25 mg/m2 on day 1 (chemoradiotherapy phase)

hydroxyurea: Each cycle: 500 mg PO q 12 hours x 6 days (11 doses)

fluorouracil: 750 mg/m2/day on days 1-5 (induction phase); 600 mg/m2/day, day 0-4 (chemoradiotherapy phase)

chemotherapy: See protocol for details

radiotherapy: See protocol for details

Chemoradiotherapy

Total

France

United States

Spain

Croatia

Russia

Region of Enrollment

Dr. Ezra E.W. Cohen

Overall Survival: Time From Randomization to Death From Any Cause

Distant Failure-free Survival (DFFS): Time From Randomization to Distant Recurrence or Death From Any Cause

Recurrence Free Survival: Time From Randomization to Local/Regional/Distant Recurrence or Death From Any Cause

Failure Pattern (Local/Regional Recurrence)

Failure Pattern (Distant Recurrence)

Survivors who completed the questionnaire. (Patients with missing data excluded.)

Quality of Life (FACT H&N)

Quality of Life (Normalcy of Diet)

Quality of Life (Speech)

Quality of Life (McMaster)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer	NCT00970502	Cancer of the P... Cancer of the L... Cancer of the N... Paranasal Sinus... Cancer of the H...	erlotinib + cel...	18 Years -	Icahn School of Medicine at Mount Sinai
Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer (DeCIDE)	NCT00117572	Cancer of the P... Cancer of the L... Cancer of the N... Paranasal Sinus... Cancer of the O...	docetaxel cisplatin hydroxyurea fluorouracil chemotherapy radiotherapy	18 Years -	University of Chicago
Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer (DeCIDE)	NCT00117572	Cancer of the P... Cancer of the L... Cancer of the N... Paranasal Sinus... Cancer of the O...	docetaxel cisplatin hydroxyurea fluorouracil chemotherapy radiotherapy	18 Years -	University of Chicago

Spots Global Cancer Trial Database for cancer of the pharynx