Induction Therapy-Docetaxel, Cisplatin and Fluorouracil in Untreated Advanced Squamous Cell or Undifferentiated Carcinoma of the Paranasal Sinuses

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”

The goal of this clinical research study is to learn if docetaxel, cisplatin, and 5-fluorouracil in combination, then followed by chemoradiotherapy is effective in controlling cancers of the paranasal sinuses.

The Study Drugs:

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 30-180 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 during the week that you receive chemotherapy treatment. At these visits, the following tests and procedures will be performed: - Blood (about 2 teaspoons) will be drawn for routine tests. - Your medical history will be recorded, including measurement of your height and weight. - Your doctor will ask about any side effects you may be experiencing. - You will have a physical exam, including measurement of your vital signs. - Your skin and inside of your mouth will be examined by your doctor. - You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation). - You will have a hearing test.

Once Cycle 2 is completed, you will have the following tests and procedures performed to learn if the disease has responded to the therapy: - Blood (about 2 teaspoons) will be collected for routine tests. - You will have a physical exam, including measurement of your vital signs. - Your medical history will be recorded, including measurement of your height and weight. - You will have a nasal endoscopy. - You will have a CT or MRI scan to check the status of the disease. - Your doctor will ask about any side effects you may be experiencing. - Your performance status will be checked. - The nerve function in your head and neck will be checked by hand. - If your doctor thinks it is necessary, you will have a chest x-ray. - If your doctor thinks it is necessary, you will have bone scans. - If your liver tests were abnormal and your doctor thinks it it is necessary, you will have a CT scan of your abdomen. - If your doctor thinks it is necessary, you will have a positron emission tomography (PET) or PET-CT. - You will have an eye exam.

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 respond 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. Before you receive the additional cycle, you will have a hearing test.

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, including measurement of your vital signs. - Your medical history will be recorded, including measurement of your height and weight. - The nerve function in your head and neck will be checked by hand. - 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, including measurement of your height and weight. - 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. - Your performance status will be checked. - One (1) time each year, blood (about 2 teaspoons) will be drawn for a thyroid function test.

If the disease responded completely while you were on study, additional tests and procedures will also be performed at 6 months during Year 1, then yearly during Years 1-3. The following tests will also be performed: - You will have an eye exam. - You will have a hearing test. - You will have a dental exam. - You will complete a questionnaire that will ask you to rate your symptoms and how much they may interfere with your daily activities. This will take about 10 minutes to complete. - You will have saliva flow tests. - You will have a CT or MRI scan to check the status of the disease. - If your doctor thinks it is necessary, you will have a chest x-ray. - If your doctor thinks it is necessary, you will have bone scans. - If your liver tests were abnormal and your doctor thinks it it is necessary, you will have a CT scan of your abdomen. - If your doctor thinks it is necessary, you will have a positron emission tomography (PET) or PET-CT.

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 nasal cavity or 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: Docetaxel, Cisplatin, and 5-Fluorouracil

Primary Measures

• Number of Patients with Complete + Partial Response
  • Time Frame: Response assessment after two 3 week cycles, then every 6 months for minimally 2 years
    Safety Issue?: No

Inclusion Criteria:

• 1. Within 12 weeks prior to study entry, patients must have a confirmed cytologic or histological diagnosis of locally advanced squamous cell carcinoma and/or poorly differentiated carcinoma of the nasal cavity and/or paranasal sinuses. If the biopsy was collected outside of MDACC, the MDACC Pathology Department must assess and confirm the SCC diagnosis.
• 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 0-1.
• 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 >/= 100,000 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. 10**
• 7. Hemoglobin >/= 10.0g/dL
• 8. Per MDACC Creatinine clearance guidelines, patients must have a 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 substantial concomitant medical illness, which in the opinion of the attending medical oncologist, would render the patient unsuitable for the study (i.e., preclude safe administration of the prescribed chemotherapy treatment).
• 10. Women Of Child Bearing Potential (WOCBP) must have a negative serum or urine pregnancy test (i.e., minimum sensitivity 25 IU/L or equivalent units of HCG), within 72 hours prior to the start of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in the study, she should inform her treating physician(s) immediately. **Refer to pg. 10 of the protocol for the formal definition of a WOCBP.**
• 11. Ability to understand and the willingness to sign a written Informed Consent Document (ICD). In the event that non-English speaking participants are eligible for this study, a short form (if applicable) or an ICD in their language, will be utilized and completed in accordance with the MDACC Policy For Consenting Non-English Speaking
• Participants.
• 12. Willingness to undergo MDACC Audiology and Ophthalmology Assessment

Exclusion Criteria:

• 1. Histology other than locally advanced squamous cell carcinoma and/or poorly differentiated carcinoma of the nasal cavity and paranasal sinuses.
• 2. Evidence of distant metastases (below the clavicle) by clinical or radiographic measures.
• 3. Karnofsky performance status < 70 or ECOG>1 (Appendices B and BB).
• 4. Pre-existing peripheral neuropathy CTCAE grade 2 or worse or pre-existing severe bilateral hearing deficits.
• 5. Prior chemotherapy (i.e., as administered strictly for cancer treatment) within the previous 3 years. Use of chemotherapy agents for non-cancer treatment purposes (i.e., arthritis treatment, etc.) are excluded from this criterion.
• 6. Prior radiotherapy to the paranasal sinus region or the upper neck (i.e., prior radiotherapy to another disease site is acceptable).
• 7. Initial surgical resection of the paranasal sinuses or nasal cavity region rendering the patient clinically and radiologically disease free.
• 8. Simultaneous primary invasive cancers or patients currently receiving any other investigational agents at time of study enrollment. Patients may have received investigational agents in the past. No washout time period is required.
• 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. Please refer to Study Appendix O for a complete list of Polysorbate 80 containing drugs.
• 13. Patients with a history of HIV or Hepatitis C.

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 Investigator: M.D. Anderson Cancer Center Other

Overall Clinical Trial Officials and Contacts

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

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

Information obtained from ClinicalTrials.gov on February 09, 2012

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