Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase I/II Study of Split-dose TPF-Induction Chemotherapy Before Surgery of Oropharyngeal and Cavity of the Mouth Cancer
Brief Summary: A combination therapy of Docetaxel, Cisplatin und 5-Fluorouracil (= TPF) will be used in patients with resectable oropharyngeal and cavity of the mouth cancer. To improve the compatibility of the TPF-induction without decreasing the efficacy the dose will be given on day 1 and 8 instead of applying the whole dose on day 1 every 3 weeks.

In the phase I-part of the trial the optimal therapeutic dose of Docetaxel and Cisplatin will be defined.

In the phase II-part the progression-free survival after 2 years will be assessed in patients treated with the optimal therapeutic dose.


Options:
A: DISEASE CHARACTERISTICS: Histologically confirmed squamous cell cancer of the head and neck suitable for treatment with radiotherapy T2, T3, or T4 primary lesions Any N No distant metastasis May also be anaplastic carcinoma, verrucous carcinoma, or transitional cell carcinoma (as of 1/97) No occult primaries (as of 1/97) No adenocarcinomas, lymphomas, or melanomas (as of 1/97) Synchronous head and neck tumors are eligible (tumor with the worse prognosis is entered into study) (as of 1/97) Patients receiving surgery to neck nodes only must be randomized as surgery patients (as of 1/97) Patients with tumors of the oral cavity or oropharynx may additionally elect randomization to nodal irradiation vs. no further therapy provided there is no second primary

PATIENT CHARACTERISTICS: Age: 75 and under for patients electing participation in the nodal vs. no nodal irradiation portion of the study Performance status: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Fit for any protocol treatment option Willing to receive any protocol treatment option Prior malignancy allowed provided the treating clinician considers the patient cured

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior therapy Chemotherapy: No prior therapy Endocrine therapy: No prior therapy Radiotherapy: No prior therapy Surgery: Prior biopsy or excision allowed
B: Inclusion Criteria:

1. Recurrent and/or metastatic head and neck squamous cell carcinoma not amenable to curative treatment with surgery and/or chemotherapy and/or radiation.
2. At least one measurable lesion by MRI or CT-scan according to RECIST 1.1.
3. Progressive disease within 1 year after first line platinum-based chemotherapy given either as a part of the multimodal curative treatment or in the palliative setting.
4. ECOG performance status 0 -2, in stable medical condition
5. Patients must have an expected survival of at least 3 months
6. Paraffin-embedded tumor tissue available for immunohistochemistry but not mandatory
7. Patients must be over 18 years old and must be able to give written informed consent.
8. Women of child-bearing age or sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine within the 7 days prior to enrollment).
9. Patients must have adequate organ function (Hemoglobin ≥ 9 g/100 ml, Neutrophils ≥ 1,500/mm3, Platelets ≥ 100,000/mm3, total bilirubin \<1 time the upper limit of normal (ULN) for age, serum alanine aminotransferase (ALT) \< 1.5 1.5 x ULN for age, aspartate aminotransferase (AST) \< 1.5 ´ ULN for age , serum creatinine \<1.5 x ULN for age.
10. Signed informed consent prior to beginning protocol specific procedure.
11. Sexually active patients must use effective contraception during the period of therapy and up to 150 days after the last treatment dose. Acceptable contraception includes, but is not limited to: oral hormone therapy, partner vasectomy, or double barrier contraception (which is defined as a male condom plus spermicide in combination with either a female condom, or diaphragm, or cervical cap or intrauterine device)

Exclusion Criteria:

1. Non-squamous head and neck cancer
2. Nasopharynx cancer
3. More than two lines of chemotherapy for palliative treatment
4. Surgery or investigational drugs or chemotherapy within 4 weeks before study inclusion. Curative radiation therapy (60-70 Gy) within 8 weeks. For palliative radiation therapy (i.e 8 Gy on a painful lesion) no delay is needed.
5. Previous treatment with cabazitaxel
6. Significant active cardiac disease including: uncontrolled high blood pressure according to the CTCAE 4 grading, unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias
7. Other uncontrolled illnesses (active infections requiring antibiotics, bleeding disorders, uncontrolled diabetes ...)
8. Previous malignancy from which the patient has been disease-free for \< 5years, as other than SCCHN.
9. Previous treatments with taxanes and/or anti-EGFR therapy are not an exclusion criteria.
10. Active grade \> 2 peripheral neuropathy
11. Active grade \> 2 stomatitis
12. Known brain or leptomeningeal involvement
13. History of severe hypersensitivity reaction (\> grade 3) to polysorbate 80 containing drugs
14. Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A/5. A one-week washout period is necessary for patients who are already on these treatments.
15. Organic brain syndrome or significant psychiatric abnormality that would preclude participation in the full protocol and follow up.
C: Inclusion Criteria:

1. Histological proven, resectable squamous epithelial carcinoma of the oropharynx and the cavity of the mouth
2. R0-resection possible
3. All T N2 M0 / all T N3 M0 / if T3 or T4a also N0-1 M0
4. Leucocytes \> 4000/mm³ bzw. neutrophils \> 2000/mm³, thrombocytes \> 100000/mm³
5. adequate kidney function, defined as serum creatinine und urea in normal range, Creatinine clearance \> 60 ml/min
6. adequate liver function with glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT) and bilirubin in normal range
7. electrolytes in normal range
8. risks of anesthesia complications normal or minor increased
9. Eastern Cooperative Oncology Group (ECOG) 0-2 / Karnofsky \>= 60%
10. Age 18 - 80 years
11. signed written informed consent
12. effective contraception for both male and female subjects if the risk of conception exists

    Exclusion Criteria:
13. T1 N0 M0 / T1 N1 M0 / T2 N0 M0 / T2 N1 M0
14. Resection without curative intention: primary tumor is not treatable with resection methods
15. Infiltration of the lower jaw
16. M1 status
17. Tumor not measurable with Innovation Center Computer Assisted Surgery (ICCAS) methods
18. No prior chemotherapy or radiation (a primary surgery is allowed)
19. Metachronous or oder synchronous malignoma (Exception: basal cell carcinoma)
20. Life expectance \< 3 months
21. ECOG \> 2; Karnofsky \< 60%
22. acute infections or fever
23. known HIV-infection or other immune suppression
24. severe cardio pulmonary concomitant diseases
25. chronic disease with continuous therapy (uncontrolled diabetes, rheumatoid arthritis) especially continuous therapy with steroids
26. other concomitant diseases which, in the investigator's opinion, would exclude the patient from the study
27. Contraindications which permit a therapy with Docetaxel, Cisplatin, 5-FU or radiation therapy
28. missing patient's compliance
29. regular Follow-up visits not possible
30. Pregnancy or lactation period
31. legal incapacity or limited legal capacity
32. Participation in another clinical trial or administration of a not approved substance within 30 days before registration
D: List of Inclusion Criteria:

* Histologically or cytologically confirmed squamous cell carcinoma of the head and neck

  * Stage III or IV\* disease
  * One of the following primary tumor sites:

    * Oral cavity

      * No mandible invasion
    * Oropharynx
    * Hypopharynx
    * Larynx
  * The following primary tumor sites are excluded:

    * Nasal cavity
    * Paranasal cavity
    * Nasopharynx NOTE: \*No evidence of distant metastases by chest x-ray, abdominal ultrasound, or CT scan (for patients with liver function test abnormalities) or bone scan (for patients with local symptoms)
* At least 1 uni- or bi-dimensionally measurable lesion

PATIENT CHARACTERISTICS:

Age

* Over 18

Performance status

* WHO 0-1

Life expectancy

* Not specified

Hematopoietic

* Neutrophil count \> 1,500/mm\^3
* Platelet count \> 100,000/mm\^3
* Hemoglobin \> 10 g/dL

Hepatic

* Bilirubin normal
* AST or ALT within eligibility range
* Alkaline phosphatase within eligibility range

Renal

* Creatinine clearance \> 60 mL/min

Cardiovascular

* No unstable cardiac disease despite treatment
* No myocardial infarction within the past 6 months

Pulmonary

* No chronic obstructive pulmonary disease, defined as requiring hospitalization for pneumonia or respiratory decompensation within the past year

  * Obstruction caused by the tumor allowed

Neurologic

* No symptomatic peripheral neuropathy \> grade 2
* No symptomatic altered hearing \> grade 2
* No history of significant neurologic or psychiatric disorders, including dementia or seizures

Other

* No active drug addiction, including alcohol, cocaine, or intravenous drugs within the past 6 months
* No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, or other cancer curatively treated by surgery alone
* No active, clinically significant, uncontrolled infection
* No autoimmune disease requiring therapy
* No unhealed or clinically active peptic ulcer disease
* No hypercalcemia
* No other serious illness or medical condition
* No involuntary weight loss \> 25% of body weight within the past 2 months
* HIV negative
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for at least 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy

Surgery

* No prior organ transplantation
* No prior surgery for this cancer

  * Biopsy allowed

Other

* More than 30 days since prior participation in another investigational study
* No other concurrent anticancer therapy

Answer: C