E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Palliative patients with metastatic and/or recurrent head and neck cancer after failure of first line standard chemotherapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the efficacy of SU011248 alone in patients with head and neck cancer in term of overall response rate (RECIST, see statistical consideration)
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E.2.2 | Secondary objectives of the trial |
Determine the safety profile of SU011248 alone in patients with head and neck cancer. Determine the efficacy of SU011248 alone in patients with head and neck cancer: progression-free survival and survival.
Part 2: 1) Determine the pharmacokinetics of SU011248 in monotherapy when administrated through a feeding tube (ie, naso-gastric or gastrostomy) in patients with head and neck cancer
2) Safety and toxicity (bleeding events, cfr. Statistical hypothesis)
3) Evaluation of tumor response by dynamic-contrasted enhanced magnetic resonance imaging
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Acceptance to participate to P-K sub-study (mandatory for part II)
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. Recurrence must be confirmed by anatomopathology (cytology or biopsy) 3. At least one measurable lesion by MRI or CT-scan 4. Failed or relapsing after first line chemotherapy including a platinum* or a taxane–based chemotherapy regimen 5. Patients ineligible for chemotherapy could be included in first line 6. ECOG performance status 0 -2, in stable medical condition 7. Patients must be able to swallow tablets 8. Patients must have an expected survival of at least 3 months 9. Paraffin-embedded tumor tissue available for immunohistochemistry 10. Patients must be over 18 years old and must be able to give written informed consent 11. Women of child-bearing age must have a negative pregnancy test 12. Female patients of child-bearing age must use effective contraception until 3 months have elapsed after the last injection 13. Patients must have normal organ function (Hemoglobin ≥ 8 g/100 ml, Neutrophils ≥ 1,500/mm3, Platelets ≥ 100,000/mm3, Serum creatinine ≤ 1.5 mg/100 ml and or creatinine clearance > 60 ml/min, Serum bilirubin ≤2.0 mg/100 ml, Aminotransferases (AST/SGOT and ALT/SGPT) must be ≤ 3x the upper institutional normal limit 14. For patients with local recurrence and easily accessible tumors, acceptance of iterative biopsies to store tumor samples (Formaldehyde for immunochemistry, RNA later) 15. Acceptance of giving 20 ml of blood for eventual pharmacogenomic analysis 16. Acceptance of giving two plasma samples (3ml) at baseline and after 4 weeks of treatment with SU011248 17. Signed informed consent prior to beginning protocol specific procedure
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E.4 | Principal exclusion criteria |
Tumor located less than 5 mm from a major arterial vessel (The imaging will be reviewed before inclusion)
1. Non-squamous head and neck cancer 2. Nasopharynx cancer 3. Brain metastases 4. More than two lines of chemotherapy for palliative treatment (except if chemotherapy was given as a part of a multimodal treatment given with a curative intent) 5. Surgery or irradiation or investigational drugs within 4 weeks before study inclusion 6. Other uncontrolled illnesses (active infections requiring antibiotics, bleeding disorders, …) 7. Active uncontrolled coronary disease or cardiac insufficiency (Ejection fraction below 40%) 8. Previous malignancy, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix 9. Other concomitant anticancer therapies 10. Previous treatment with anti-VEGF, PDGF, or kit therapies. EGFR therapy is not an exclusion criteria. 11. Organic brain syndrome or significant psychiatric abnormality that would preclude participation in the full protocol and follow up.
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E.5 End points |
E.5.1 | Primary end point(s) |
Amendment 5:
To assess the pharmacokinetics of SU011248 while administered through the feeding tube (naso-gastric or gastrostomy) in patients not able to swallow (in comparison with patients taking SU011248 .
Determine the efficacy of SU011248 alone in patients with head and neck cancer in term of overall response rate (RECIST, see statistical consideration).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 0 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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A month after the last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |