E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
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 |
Progression-free survival (PFS) by independent central review (ICR), based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) |
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E.2.2 | Secondary objectives of the trial |
• Objective response rate (ORR) • Disease control rate (DCR) • Overall survival (OS) • PFS according to Investigator assessment of radiologic images • Safety and tolerability
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Study Title: Clinical Validation Study: Evaluation of the TruSight™ Oncology Comprehensive Assay in detecting FGFR2 gene rearrangements in cholangiocarcinoma for treatment of patients with futibatinib Protocol Number: ONCO-T05-009 Date: 06 April 2021 Version: 1 |
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E.3 | Principal inclusion criteria |
1. Provide written informed consent. 2. Is ≥ 18 years of age (or meets the country’s regulatory definition for legal adult age). 3. The patient has histologically confirmed, locally advanced, or metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements based on testing performed by the designated central laboratory. 4. Patient has radiographically measurable disease per RECIST 1.1. 5. Patients who have received treatment for locally advanced disease (for example, trans-arterial chemoembolization, selective internal radiation therapy, external beam radiation) must have evidence of radiographic progression with measurable disease outside the previously-treated lesions. 6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. 7. Adequate organ function as defined by the following criteria: • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT ≤ 5 × ULN. • Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert’s syndrome. • White blood cell (WBC) count ≥ 2000/mm3 (≥ 2.0 × 109/L) • Absolute neutrophil count (ANC) ≥ 1000/mm3 (ie, ≥ 1.0 × 109/L) • Platelet count ≥ 100,000/mm3 (≥ 100 × 109/L) • Hemoglobin ≥ 9.0 g/dL • Phosphorus ≤ 1.5 × ULN • Creatinine clearance ≥ 60 mL/min 8. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of the first dose of study medication. Female patients are not considered to be of child bearing potential if they have a history of hysterectomy or are post menopausal defined as no menses for 12 months without an alternative medical cause. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose and for 3 months after the last dose of study therapy, or according to the local label for each study therapy (whichever is longer). 9. Willing and able to comply with scheduled visits and study procedures. |
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E.4 | Principal exclusion criteria |
1. Patient has received previous systemic anticancer therapy • Patients receiving adjuvant or neoadjuvant treatment and completed ≥6 months prior to randomization are eligible 2. Patient has mixed hepatocellular carcinoma – iCCA disease. 3. History and/or current evidence of any of the following disorders: • Non-tumor related alteration of calcium-phosphorus homeostasis that is clinically significant in the opinion of the Investigator. • Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator. • Retinal disorder confirmed by retinal examination and considered clinically significant in the opinion of the ophthalmologist. 4. History or current evidence of uncontrolled ventricular arrhythmias 5. Fridericia’s corrected QT interval (QTcF) > 470 ms on ECG conducted during Screening. 6. Treatment with any of the following within the specified time frame prior to the first dose of study therapy, or failure to recover from side effects of these prior therapies: • Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of study therapy). • Radiotherapy (any dose) for extended field within 4 weeks or limited field radiotherapy within 2 weeks, and/or has not recovered from acute impact of radiotherapy. • Patients with locoregional therapy, e.g. transarterial chemoembolization, selective internal radiotherapy, or ablation within 4 weeks. • Any history of liver transplant. 7. A serious illness or medical condition(s) including, but not limited to, the following: • Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month). • Known acute systemic infection. • Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the previous 6 months. • Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the Investigator. • Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death. • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the Investigator would make the patient inappropriate for entry into this study. 8. Patients with a history of another primary malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the Investigator. 9. Pregnant or breast-feeding female 10. The patient is unable to take oral medication. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) per ICR central assessment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of every 2 cycles (± 7 days) up to Cycle 4. Thereafter, every 3 cycles (± 7 days), or as clinically indicated, until radiologic progressive disease (PD) or initiation of new anticancer therapy (whichever occurs first). |
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E.5.2 | Secondary end point(s) |
Secondary endpoints: • Objective response rate (ORR) • Disease control rate (DCR) • Overall survival (OS) • PFS according to Investigator assessment of radiologic images • Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), clinical laboratory tests, vital signs, ophthalmological exams, and 12-lead electrocardiogram (ECG). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Bullet point 1-4: At the end of every 2 cycles (± 7 days) up to Cycle 4. Thereafter, every 3 cycles (± 7 days), or as clinically indicated, until radiologic progressive disease (PD) or initiation of new anticancer therapy (whichever occurs first).
Bullet point 5: All throughout the study, from the time main informed consent is signed through 30 days after administration of the last dose of study therapy or until the start of new anticancer therapy, whichever is earlier. |
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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 | Yes |
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 |
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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 | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
Argentina |
Australia |
Brazil |
China |
Hong Kong |
Japan |
Korea, Republic of |
Mexico |
Peru |
Taiwan |
Thailand |
United States |
France |
Poland |
Netherlands |
Spain |
Germany |
Italy |
Belgium |
Portugal |
United Kingdom |
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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
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The end of the trial occurs after study completion, and is defined as the time when the last patient has discontinued study treatment (including patients in the Study Extension phase, if applicable) and completed all visits and scheduled procedures. |
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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 | 7 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |