Official Title: “Phase II Trial of Induction Therapy With Docetaxel, Cisplatin and Fluorouracil in Previously Untreated Patients With Locally Advanced Squamous Cell or Undifferentiated Carcinoma of the Paranasal Sinuses”

Primary Objectives: - To determine the clinical/radiographic complete and partial response rate after induction chemotherapy with docetaxel, cisplatin and fluorouracil (TPF) - To improve local tumor control to 80% at 2 years

Secondary Objectives: - Disease specific-survival and overall survival rates - Organ preservation (orbital, maxillary, cranial) rate - Patterns of treatment failure (local, regional, and distant) - Acute and late treatment-related toxicity - The effect of treatment on Quality of Life with and without surgery - To evaluate the effects of induction chemotherapy on biological markers that could serve as surrogates for response and predictors of long-term outcome.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2011

The Study Drug - Docetaxel is designed to stop the growth of cancer cells, which may cause the cells to die. It is believed to be weakly effective at killing blood vessels in cancer cells as well. - Cisplatin has an atom at its center that contains platinum. The platinum is supposed to poison the cancer cells, which may cause them to die. - 5-Fluorouracil is designed to destroy cancer cells by preventing them from dividing and multiplying.

Study Drug Administration

If you are found to be eligible to take part in this study, you will receive 5-fluorouracil through a needle in your vein, non-stop, on Days 1-4 of each 21-day study "cycle". On Day 1 only, you will receive docetaxel over 1 hour and cisplatin over 30-120 minutes. You will receive 2-3 cycles of therapy. If you are having side effects, the study doctor may schedule you to receive the study drugs on a longer cycle.

Study Visits

During Weeks 1-3 of Cycles 1 and 2, you will have study visits every week. At these visits, the following tests and procedures will be performed: - Blood (about 2 teaspoons) will be drawn for routine tests. - Your weight will be measured. - Your doctor will ask about any side effects you may be experiencing. - You will have a physical exam. - Your skin and inside of your mouth will be examined by your doctor.

Once Cycle 2 is completed, you will have the following tests and procedures performed to learn if the disease has responded to the therapy: - You will have a physical exam. - You will have a nasal endoscopy. - You will have an MRI. - Your doctor will ask about any side effects you may be experiencing. - If your doctor thinks it is necessary, you will have a CT scan.

Chemotherapy or Radiotherapy

Based on the results of the tests and procedures performed to check to see if the disease has responded, your doctor will decide your next treatment.

If you respond partly or completely, you will receive a 3rd cycle of chemotherapy. You will follow the same schedule as you did during the first 2 cycles. Once you complete the 3 cycles of chemotherapy, you will begin chemoradiation. Your doctor will discuss this with you in more detail and you will receive a separate consent form.

If the disease does not responded partly or completely, you will have surgery followed by radiotherapy. Before surgery you will be asked to sign a separate informed consent. Risks will be discussed with your treating doctor and will depend on the type of surgery. Before radiotherapy you will be asked to sign a separate informed consent that will describe possible risks.

Additional Cycles

If the disease responds partly or completely, you will receive an additional (third) cycle of therapy. If you have the additional cycle, you will follow the same schedule as you did during Cycles 1 and 2.

Study Visit After Chemoradiation

If you receive chemoradiation, after your last chemotherapy treatment you will have the following tests and procedures performed: - You will have a physical exam. - You will have a nasal endoscopy. - You will have an MRI. - Your doctor will ask about any side effects you may be experiencing. - If your doctor thinks it is necessary, you will also have a CT or positron emission tomography (PET)-CT scan.

Length of Study

You will remain on study treatment for 16-20 weeks. You will be taken off study early if the disease gets worse or intolerable side effects occur.

Follow-up/End-of-Treatment Visits If the disease responded completely while you were on study, you will have follow-up visits every 3 months during Years 1-2, every 4 months during Year 3, and every 6 months during Years 4-5. If the disease did not respond completely and you are having side effects at the end-of-study visit, you will have follow-up visits every 4 weeks until the side effects go away. At each visit, the following tests and procedures will be performed: - Your complete medical history will be recorded. - You will have a physical exam, including measurement of your vital signs. - You will have a nasal endoscopy. - The nerve function in your head and neck will be checked. - Your doctor will ask about any side effects you may be experiencing. - One (1) time each year, blood (about 2 teaspoons) will be drawn for a thyroid function test.

Additional information

At any time during the study, you will have an MRI if your doctor thinks it is necessary.

This is an investigational study. Docetaxel is FDA approved for the treatment of certain types of breast cancer, gastric cancer, prostate cancer, and advanced squamous cell carcinoma of the head and neck.

Cisplatin is FDA approved to be used together with other drugs to treat advanced ovarian cancer, testicular cancer, locally advanced squamous cell carcinoma of the head and neck, late-stage cervical cancer, and non-small cell lung cancer.

5-fluorouracil is FDA approved to be used with other drugs to treat metastatic colorectal cancer, locally advanced squamous cell carcinoma of the head and neck, and gastric adenocarcinoma.

The use of these drugs to treat cancer of the paranasal sinuses is investigational.

Up to 45 patients will take part in this study. All will be enrolled at M. D. Anderson.

Intervention(s) in this Clinical Trial

• Drug: Docetaxel
  • 75 mg/m^2 IV on day 1 of each cycle.
• Drug: 5-Fluorouracil
  • 750 mg/m^2 continuous infusion on days 1 through 4 of each cycle.
• Drug: Cisplatin
  • 75 mg/m^2 IV over 30-120 minutes on day 1 of each cycle.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Docetaxel, Cisplatin, and 5-Fluorouracil

Primary Measures

• To learn if docetaxel, cisplatin, and 5-fluorouracil in combination can help to control the disease in patients with cancer of the paranasal sinuses.
  • Time Frame: 3 Years
    Safety Issue?: No

Inclusion Criteria:

• 1. Patients with cytologic or histological diagnosis of squamous cell carcinoma or poorly differentiated carcinoma of the nasal cavity and paranasal sinuses.
• 2. 2. Stage II-IV disease; T 2-4, N any, M0. Measurable disease is required with the following criteria: Measurable lesions can be accurately measured, with at least one diameter >\= 1.0 cm by spiral CT scan or MRI. Lesions can be bidimensionally measurable or unidimensionally measurable. Every effort should be made to measure lesions in two dimensions. Measurable disease is present if the patient has one or more measurable lesions.
• Non-measurable lesions/disease are all other lesions, including small lesions (those with measurements < 2.0 cm; or < 1.0 cm with spiral CT).
• 3. Karnofsky performance status of >\= 70 or ECOG PS 0-2.
• 4. Age > 16 years.
• 5. Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC) of >/= 1500 cells/mm3 and platelet count of >/= 140,000 cells/mm3;
• 6. Hepatic Parameters: Total Bilirubin </= ULN AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used. **Refer to table in protocol pg.6**
• 7. Hemoglobin >/= 10.0g/dL
• 8. Creatinine clearance > 50 ml/min determined by 24 hour collection or nomogram: CrCl male = (140 - age) x (wt in kg)/serum Cr x 72 CrCl female = 0.85 x (CrCl male)
• 9. Patients should have no debilitating acute or chronic co-morbid condition, or acute serious infection that in the opinion of the attending medical oncologist would preclude safe administration of the prescribed chemotherapy treatment.
• 10. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.
• 11. Patients must sign a study-specific informed consent form.

Exclusion Criteria:

• 1. Histology other than squamous cell or poorly differentiated carcinoma.
• 2. Evidence of distant metastases (below the clavicle) by clinical or radiographic measures.
• 3. Karnofsky performance status < 70 or ECOG>2 (Appendices B and BB).
• 4. Pre-existing peripheral neuropathy CTCAE grade 2 or worse or pre-existing severe bilateral hearing deficits.
• 5. Prior chemotherapy, within the previous 3 years.
• 6. Prior radiotherapy to the paranasal sinus region or the upper neck.
• 7. Initial surgical resection rendering the patient clinically and radiologically disease free.
• 8. Simultaneous primary invasive cancers.
• 9. Patients with a past history of malignancy (excluding non melanoma skin cancers, and cancers treated > 3 years prior for which patient remains continuously disease free).
• 10. Men and Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 3 months after the study. Subjects who are men must also agree to use effective contraception. Note: WOCBP must be using an adequate method of contraception throughout the study and for up to 3 months after the study. Adequate methods of contraception will include (oral, injectable, or implantable hormonal contraceptive;
• tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner).
• 11. Women who are pregnant or breastfeeding.
• 12. Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 17 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Ehab Y. Hanna, MD Principal Investigator U.T. M.D. Anderson Cancer Center  

Overall Contact: Ehab Y. Hanna, MD 713-745-2672 

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00707473

Study ID Number: 2007-0433

ClinicalTrials.gov Identifier: NCT00707473

Health Authority: United States: Institutional Review Board

UT MD Anderson Cancer Center