E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gatrointestinal stromal tumor (GIST) |
|
E.1.1.1 | Medical condition in easily understood language |
Malignant tumor disease arising from the gastrointestinal tract (e.g., stomach, intestine) belonging to the sarcoma group of tumors |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Calculate the disease control rate (DCR)=complete remission (CR)+partial remission (PR) + stable disease (SD) at 12 weeks |
|
E.2.2 | Secondary objectives of the trial |
1. Calculate overall response rate (ORR=CR+PR) at the time of best response since start of pazopanib
2. Calculate progression free survival (PFS) for patients administered pazopanib
3. Calculate DCR in relation to mutational status of primary tumor sample
4. Calculate DCR in relation to plasma concentration at week 12
5. Assess the toxicity in patients treated with pazopanib |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a) metastatic and/or locally advanced GIST
b) measurable disease as defined by RECIST
c) progressive disease after both imatinib and sunitinib treatment, and also after nilotinib if this drug ha been given
d) no other tyrosin kinase inhibitors given than imatinib, sunitinib, and nilotinib
e) age at least 18 years
f) WHO performance status 0-2
g) resolution of toxic side effects from earlier treatment
h) sufficient organ functions as defined in the protocol
i) acceptence to use adequate contraception throughout the study period for women with childbearing potential
j) written informed consent |
|
E.4 | Principal exclusion criteria |
a) prior malignancy if claiming active treatment or otherwise is judged to be of significance for the study treatment
b) clinically significant gastrointestinal bleeding
c) uncontrolled infection of significance
d) major surgery or trauma within 28 days priot to the start of study treatment
e) active bleeding or bleeding diathesis
f) endobronchial lesions or lesions infiltrating major pulmonary vessels
g) medical, psychiatric or other condition that could interfere with safety or compliance
h) pregnancy or lactation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Disease control rate (DCR=CR+PR+SD) at 12 weeks from start of pazopanib treatment according to RECIST version 1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks from start of treatment |
|
E.5.2 | Secondary end point(s) |
1. Overall response rate (ORR) defined as the fraction of patients ever achieving CR or PR during protocol treatment
2. Progression free survival (PFS) defined as the time from start of pazopanib to progressive disease according to RECIST version 1.1
3. DCR in relation to mutational status of primary tumor sample
4. DCR in relation to plasma concentration of pazopanib at week 12 of treatment
5. Toxicity defined as adverse events and abnormal laboratory test results |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For 1, 2, and 5 above - continously during protocol treatment; for 5 also including 30 days after end of treatment
For 3 and 4 - at week 12 of treatment |
|
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 | 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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 15 |
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 | 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
|
30 days after end of treatment for last patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
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 | 1 |
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 |