E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Solid Tumors including Lymphomas |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of eribulin mesylate administered as an intravenous infusion on Day 1 and Day 8 of a 21-day cycle to children with refractory or recurrent solid tumors [excluding central nervous system (CNS)], including lymphomas.
To define and describe the toxicities of eribulin mesylate administered on this schedule.
To characterize the pharmacokinetics of eribulin mesylate in children with refractory or recurrent cancer.
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E.2.2 | Secondary objectives of the trial |
To preliminarily define the antitumor activity of eribulin mesylate within the confines of a Phase 1 study.
To characterize the pharmacokinetics of eribulin mesylate in infants with refractory or recurrent cancer.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Participants must be greater than or equal to 12 months and less than 18 years of age at the time of study enrollment.
-Participants must be greater than 6 months and less than 12 months of age at the time of study enrollment. Participants will enroll one dose level behind the dose level at which Participants in Part A1 are enrolling.
-Participants with refractory or recurrent solid tumors or lymphomas, excluding CNS tumors, are eligible. Participants must have had histologic -verification of malignancy at original diagnosis or relapse. Participants with primary CNS tumors, known CNS metastases, or a prior history of CNS metastases are not eligible.
-Participants must have either measurable or evaluable disease.
-Participant's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
Note: the list is not exhaustive.
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E.4 | Principal exclusion criteria |
-Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective double barrier contraceptive method for the entire period in which they are receiving protocol therapy.
-Participants receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
-Participants who are currently receiving another investigational drug are not eligible.
-Participants who are currently receiving other anticancer agents are not eligible.
-Participants who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
Note: the list is not exhaustive.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. MTD and/or RP2D of eribulin mesylate administered as an intravenous infusion
2. Number of Adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, as a measure of safety and tolerability
3. Pharmacokinetics of eribulin mesylate: Maximum observed concentration (Cmax)
4. Pharmacokinetics of eribulin mesylate: Time to achieve maximum concentration Cmax (tmax)
5. Pharmacokinetics of eribulin mesylate: Area under the concentration vs time curve (AUC)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Days 1 and 8 of a 21-day cycle
2, 3, 4, and 5: Up to 5 days
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E.5.2 | Secondary end point(s) |
1. Evaluation of disease response to preliminarily define the antitumor activity of eribulin
2. Pharmacokinetics of eribulin mesylate in infants with refractory or recurrent cancer: Cmax
3. Pharmacokinetics of eribulin mesylate in infants with refractory or recurrent cancer: tmax
4. Pharmacokinetics of eribulin mesylate in infants with refractory or recurrent cancer: AUC
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | Yes |
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 |
Maximum tolerated dose (MTD) /recommended Phase 2 dose (RP2D) and pharmacokinetics |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | No |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
An interventional clinical trial with one or more arms and pre-specified outcome measures |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA 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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E.8.9 Initial estimate of the duration of the trial |
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 |