E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically confirmed differentiated or medullary thyroid cancer by local pathologist. |
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E.1.1.1 | Medical condition in easily understood language |
Patient with Thyroid cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027105 |
E.1.2 | Term | Medullary 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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066474 |
E.1.2 | Term | 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 | 20.0 |
E.1.2 | Level | PT |
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 |
The primary objective is to explore the efficacy of nintedanib (as measured by progression free survival) as second line therapy for patients with either differentiated or medullary thyroid cancer progressing after first line therapy. |
|
E.2.2 | Secondary objectives of the trial |
♦ To explore the safety of nintedanib as second line treatment in patients with MTC or DTC.
♦ To explore the molecular mechanisms of action of the drug.
♦ To explore other measure of activity/efficacy i.e. overall survival, duration of response, PFS at second progression (PFS-2) for patients crossing over from placebo to nintedanib. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
♦ Histologically confirmed differentiated or medullary thyroid cancer by local pathologist.
♦ Available tumor tissue at the time of initial diagnosis for histology review.
♦ Locally advanced or metastatic disease deemed incurable by surgery, radiotherapy and/or radioactive iodine (RAI).
♦ Patients must have measurable lesion with documented progression during the 12 months prior to randomization.
♦ Patients must have received one or 2 prior line of treatment (but no more than two) and must be off treatment for at least 4 weeks prior to randomization. Patients with an MTC must have received one or 2 prior line of treatment (but no more than two) and must be off treatment for at least 4 weeks prior to randomization. If it is available and reimbursed in the respective country one of the prior lines of treatment needs to be with Vandetanib as long as there is no contraindication or the patient refuses the treatment with Vandetanib.
♦ Age ≥18 years.
♦ Performance status (PS) 0-1 (WHO, Appendix C).
♦ Life expectancy of more than 12 weeks.
♦ Adequate organ function, evidenced by the following laboratory results within 3 weeks prior to randomization
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E.4 | Principal exclusion criteria |
♦ Current symptomatic brain metastases or if previously present, must have been treated at least two months before randomization.
♦ History of other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin.
♦ Ongoing treatment related toxicity due to prior treatment > grade I (except alopecia).
♦ History of significant cardiac disease
♦ Current uncontrolled hypertension
♦ Evidence of active bleeding or bleeding diathesis.
♦ Cerebrovascular accident at any time in the past, transient ischemic attack, deep venous thrombosis (DVT) or pulmonary embolism in the past 6 months
♦ History of clinically significant gastrointestinal disorders .
♦ Current severe, uncontrolled systemic disease or any other systemic disease/symptom that can hamper compliance with the protocol.
♦ Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery.
♦ History of receiving any investigational treatment within 28 days prior to randomization
♦ Women or patients of child bearing potential who do not use any contraceptive methods
♦ Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
♦ Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients of nintedanib. |
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E.5 End points |
E.5.1 | Primary end point(s) |
♦ Progression free survival (RECIST 1.1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients be followed every 8 weeks until progression for the endpoints of the trial |
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E.5.2 | Secondary end point(s) |
♦ Response Rate (RECIST 1.1)
♦ Duration of response
♦ Exploration of the molecular mechanisms of action of drug
♦ PFS at second progression (PFS-2) for patients crossing over from placebo to nintedanib.
♦ Toxicity profile (CTCAE version 4.0 will be used for adverse event reporting)
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|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients be followed every 8 weeks until progression for the endpoints of the trial |
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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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
End of study occurs when all of the following criteria have been satisfied:
1. Thirty days after all patients have stopped protocol treatment
2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
3. The database has been fully cleaned and frozen for this analysis |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |