E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
recurrent/advanced follicular, papillary or anaplastic thyroid cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016935 |
E.1.2 | Term | Follicular thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002240 |
E.1.2 | Term | Anaplastic thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033701 |
E.1.2 | Term | Papillary thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
•Follicular and papillary thyroid cancer (DTC): efficacy measured by tumor response rate
•Anaplastic thyroid cancer (ATC): efficacy measured by disease control rate after 2 cycles
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E.2.2 | Secondary objectives of the trial |
•efficacy variables including: duration of response, duration of stable disease (especially for ATC), time to progressive disease (TTP), survival time • toxicity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of metastatic, histologically proven follicular/papillary or anaplastic thyroid cancer without clinically meaningful surgical or radiotherapeutic options and/or no amenability for radio-iodine therapy. 2. No other forms of chemotherapy or investigational anticancer agents therapy for at least 4 weeks before enrollment in study. 3. Performance status of 0 to 2 on the ECOG scale (Protocol Appendix B). 4. Evidence of measurable disease according to the RECIST criteria, which means: Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable as follows:
X-ray, physical exam > 20 mm Spiral CT scan > 10 mm Non-spiral CT scan > 20 mm All radiology studies must be performed within 28 days prior to registration (35 days if negative). 5. Prior radiation therapy and surgery allowed if completed at least 2 weeks prior to study enrollment, prior radioiodine treatment at least 3 months prior to study enrollment and patients must have recovered from the acute toxic effects of the treatment prior to study entry. 6. Adequate organ function including the following: • Adequate bone marrow reserve: platelets 100 x 109/L, hemoglobin 9 g/dl, absolute granulocyte count (AGC) >1.5 x 109/L. • Hepatic: bilirubin 1.5 times upper limit of normal, aspartate transaminase (AST) and alanine transaminase (ALT) 3.0 times normal (AST and ALT 5.0 times normal is acceptable if due to liver metastases). • Renal: calculated creatinine clearance 45 ml/min, using MDRD-formula (see http://nephron.com/cgi-bin/MDRDSIdefault.cgi) 7. No active infection (at the discretion of the investigator) or current central nervous system (CNS) metastases or history of central nervous system metastases or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator). 8. No breast feeding nor pregnancy. For women of childbearing potential a negative serum pregnancy-test has to be performed 7 days prior to inclusion into the study. 9. No coexisting second malignancy or history of prior malignancy within the last 5 years. (Excluding basal or squamous cell carcinoma of the skin, superficial bladder cancer and in situ carcinoma of the cervix with no evidence of recurrence). 10. For men and women of childbearing potential appropriate contraceptive precautions should be taken during the trial and for 3 months afterwards. 11. No significant cardiovascular disease in the form of abnormal electrocardiogram (ECG) coupled with clinical features of recent or recurrent symptomatic cardiac disease (including myocardial infarction within the last year, uncontrolled angina, arrhythmia or hypertension, severe congestive heart failure (NYHA >3)). 12. No evidence of peripheral neuropathy greater than CTC Grade 1. 13. No prior taxane and/or pemetrexed (Alimta) therapy. 14. Ability to discontinue administration of acetysalicylate (Aspirin®) and other nonsteroidal anti-inflammatory agents (NSAID) in case of higher daily dosages (e.g. > 1.3 g), the day of, for 2 days before, and 2 days after the dose of pemetrexed (Alimta) (5 days prior for long-acting agents such as piroxicam).Exceptions for selective cyclooxygenase II-inhibitors in analgesic treatment may be discussed. 15. No clinically significant effusions (pleural or peritoneal), or albumin <2.5 g/dl at the time of study treatment application. The drainage of effusions prior to study treatment application is possible. 16. Inability of oral intake of folic acid or intramuscular vitamin B12 supplementation. 17. At least 18 years of age and absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial 18. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. 19. Participation in another trial at the same time is not allowed.
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E.4 | Principal exclusion criteria | |
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint of the study is the measurement of the objective response rate. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | No |
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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Patients will be treated until progression of disease, a follow up period of 1 year after Last patients end of treatment is planned. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |