E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal Cell Carcinoma Stage III,
Renal Cell Carcinoma Stage IV,
Metastatic Renal Cell Carcinoma, |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038400 |
E.1.2 | Term | Renal carcinoma stage IV |
E.1.2 | System Organ Class | 100000004864 |
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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 | 10038399 |
E.1.2 | Term | Renal carcinoma stage III |
E.1.2 | System Organ Class | 100000004864 |
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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 | 10050076 |
E.1.2 | Term | Metastatic renal carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To allow continued access to tivozanib for subjects who have participated in other tivozanib (monotherapy or combination) protocols, who are tolerating study drug and displaying clinical benefit.
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E.2.2 | Secondary objectives of the trial |
To assess long-term safety and tolerability in subjects who continue on tivozanib
To determine the duration of response and progression-free survival (PFS) of subjects who continue on tivozanib
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject must have received tivozanib while enrolled in another protocol, must be tolerating study drug and must currently display clinical benefit.
2. If female of childbearing potential, documentation of negative pregnancy test prior to enrollment.
3. Ability to give written informed consent
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E.4 | Principal exclusion criteria |
1. > 4 weeks since discontinuation of treatment on a previous protocol
2. Pregnant or lactating
3. Sexually active male and pre-menopausal female subjects (and their partners) unless they agree to use adequate contraceptive measures, while on study and for 30 days after the last dose of study drug.
4. Uncontrolled hypertension
5. Newly identified CNS malignancies or documented progression of CNS metastases
6. Unhealed wounds (including active peptic ulcers)
7. Serious/active infection or infection requiring parenteral antibiotics
8. Life-threatening illness or organ system dysfunction compromising safety evaluation
9. Psychiatric disorder, altered mental status precluding informed consent or necessary testing
10. Inability to comply with protocol requirements
Drugs and treatments to be excluded and dietary restrictions during study participation
The following medications are prohibited:
1. Agents targeting the VEGF pathway
2. Chemotherapy, other signal transduction inhibitors, monoclonal antibodies, immunotherapy or biological response modifiers (if taken as part of parent protocol then allowed).
3. Systemic hormonal therapy, during the study with the exception of:
• Hormonal therapy for appetite stimulation or contraception
• Nasal, ophthalmic, inhaled and topical steroid preparations
• Androgen suppression therapy for non-metastatic prostate carcinoma
• Hormone replacement therapy for conditions such as adrenal insufficiency, hypothyroidism, etc
• Low-dose maintenance steroid therapy (equivalent of prednisone ≤ 10mg/day) for other conditions
4. Treatment with radiotherapy (limited radiotherapy involving < 25% of bone marrow may be allowed for palliative purposes after consultation with the medical monitor, treatment with study drug must be stopped during radiotherapy).
5. Herbal preparations/supplements (including daily multivitamin/mineral supplement containing herbal components).
6. Treatment with cytochrome P450 (CYP3A4) inducers or inhibitors (see Appendix A for examples).
7. Treatment with full-dose oral anticoagulants such as warfarin, acenocoumarol, fenprocoumon, or similar agents (full dose anticoagulation with low molecular weight heparin or unfractionated heparin administered subcutaneously, or low dose oral anticoagulation that does not increase INR >1.5 X ULN, are allowed).
8. Grapefruit and grapefruit juice |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
allow continued access to tivozanib |
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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 | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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The end of the study is the last treatment visit of the last subject at the last site.The protocol will continue until tivozanib hydrochloride becomes commercially available in each country. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |