E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fibroblast growth factor receptor (FGFR) aberrations |
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E.1.1.1 | Medical condition in easily understood language |
solid tumors or gastric 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 | LLT |
E.1.2 | Classification code | 10007050 |
E.1.2 | Term | Cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Cohorts A nd B :The primary objective is to evaluate the objective response rate (ORR) in patients with solid tumors harboring FGFR rearrangements or gastric cancer (including GEJ cancer) harboring FGFR2 amplifications based on independent central review of radiologic images (IRC).
Cohort C: The overall objective of Cohort C is to assess the clinical activity of futibatinib as monotherapy in the treatment of patients with myeloid/lymphoid neoplasms (MLN) harboring FGFR1 rearrangements. |
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E.2.2 | Secondary objectives of the trial |
Cohorts A and B Secondary objectives include assessment of: - ORR based on Investigator assessment; - Disease control rate (DCR); - Duration of response (DOR); - Progression-free survival (PFS); - Overall survival (OS); and - Safety and tolerability.
Cohort C Secondary objectives include assessment of: -ORR -CR + complete response, and overall survival with incomplete hematological recovery (CRi) rate -Complete or partial cytogenetic responses (CCyR or PCyR) rate -Duration of CR -Duration of CR+CRi -DOR -Time-to-events -To assess the safety and tolerability
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Study submitted via new IRAS system |
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E.4 | Principal exclusion criteria |
Study submitted via new IRAS system |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cohorts A and B Objective response rate is defined as the proportion of patients with objective evidence of CR or PR. The primary evaluation of ORR will be based on an independent central review of radiologic images. At the analysis stage, the best objective response will be assigned for each patient as the best response recorded after initiation of study treatment and confirmed at least 4 weeks later. If applicable, responses recorded after disease progression or initiation of new anticancer treatment will be excluded. The exact 2-sided CI based on Clopper-Pearson methodology will be derived for ORR. Cohort C Complete response rate defined as the proportion of patients who achieved a CR will be calculated and the exact 2-sided CI will also be derived using the Clopper Pearson methodology. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
A patient will be discontinued from all study therapy for any of the following reasons: 1.Disease progression 2.Unacceptable AEs, or change in underlying condition such that the patient can no longer tolerate therapy, as evidenced by a dose delay > 28 days from the scheduled start date of the next cycle or need for more than 2 dose reductions outlined in this protocol 3.Physician’s decision, including need for other anticancer therapy not specified in the protocol or surgery or radiotherapy to the only site(s) of disease being followed in the study 4.Pregnancy 5.Termination of the study by the Sponsor, or 6.At the patient’s request at any time irrespective of the reason.
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E.5.2 | Secondary end point(s) |
Cohorts A and B : Secondary Endpoints -Overall response rate based on investigator assessment will be determined as described above for the primary analysis of ORR based on independent central review of radiologic images -Disease control rate will be analyzed using the same methodology as ORR -Duration of response will only be evaluated in patients with an objective response of CR or PR. Patients who are alive and progression-free as of the analysis cut-off date will be censored at their last evaluable tumor response assessment prior to initiation of any new anticancer treatment. Patients who start subsequent anticancer therapy without a prior reported progression will be censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy -Progression-free survival will be estimated using the Kaplan-Meier method. Patients who die without a reported disease progression will be considered to have progressed on the date of their death. Patients who did not progress or die will be censored on the date of their last tumor assessment. Patients who did not have any on-study assessments and did not die will be censored on the first dosing date. Patients who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. -Overall survival will be analyzed in a similar manner to PFS. In the absence of confirmation of death or for patients who are alive as of the OS cut-off date, survival time will be censored at the last known date that the patient was alive.
Cohort C: Secondary Endpoints -The overall response, CR+CRi (leukemia presentation only), CCyR, and PCyR rates will be calculated and the exact 2-sided CIs will also be derived using the Clopper-Pearson methodology. -Duration of CR (only in patients who achieved a CR), duration of CR+CRi (only in patients who achieved a CR/CRi [leukemia presentation only]), and duration of response (only in patients with an objective response of CR, CRi [leukemia presentation only], or PR) will be estimated using the Kaplan-Meier method. Patients who are alive and progression-free as of the analysis cut-off date will be censored at their last evaluable tumor response assessment prior to initiation of any new anticancer treatment. Patients who start subsequent anticancer therapy without a prior reported progression will be censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. -Progression-free survival will be estimated using the Kaplan-Meier method. Patients who die without a reported disease progression will be considered to have progressed on the date of their death. Patients who did not progress or die will be censored on the date of their last tumor assessment. Patients who did not have any on-study assessments and did not die will be censored on the first dosing date. Patients who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. -Relapse-free survival will only be evaluated in patients with an objective response of CR and measured from the first date of achieving CR until the first date of relapsed disease or death from any cause, whichever occurs first. Patients who die without a reported disease relapse will be considered to have relapsed on the date of their death. Patients who did not relapse or die will be censored on the date of their last tumor assessment. Patients who started any subsequent anti-cancer therapy without a prior reported relapse will be censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. -Event-free survival will be estimated only for patients with leukemia presentation using the Kaplan-Meier method. EFS is defined as the time from first dose of study therapy to treatment failure, relapse after CR (if applicable), or death from any cause, whichever occurs first. For a patient with none of these events before the end of study follow-up, observation of EFS is censored at the date of last contact prior to the analysis cut-off date. If the patient does not achieve a CR, EFS is defined as the point of treatment failure or death, whichever comes first. Treatment failure for EFS is defined as PD in this study. -Overall survival will be analyzed in a similar manner to PFS. In the absence of confirmation of death or for patients who are alive as of the OS cut-off date, survival time will be censored at the last known date that the patient was alive. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment will continue until disease progression, unacceptable toxicity, or any other of the criteria for treatment discontinuation is met. |
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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 | No |
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 | 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) | 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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 38 |
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 |
Belgium |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Portugal |
Singapore |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
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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 trial will occur when all patients (including patients in the Study Extension phase, if any) have discontinued treatment and undergone all protocol-mandated assessments (including the 30-day safety follow-up visit). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |