| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
Solid tumours in young patients
|
|
| 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 | 10065252 |
| E.1.2 | Term | Solid tumor |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 determine the maximum tolerated dose (MTD) and recommend a Phase 2 dose of sunitinib administered orally once daily for 28 days followed by 14 days rest period in children with refractory solid tumours.
- To define and describe the toxicities of sunitinib administered on this schedule.
- To characterize the pharmacokinetics of oral sunitinib in children with refractory solid tumours.
- To evaluate the tolerability and pharmacokinetic profile of sunitinib capsule contents sprinkled over applesauce or yoghurt using the recommended phase 2 dose from the phase 1 component of this trial.
|
|
| E.2.2 | Secondary objectives of the trial |
- To determine, in a preliminary manner, the antitumour effects of oral sunitinib in children with refractory solid tumours.
- To describe changes in peripheral blood monocyte counts, circulating endothelial cells, and plasma angiogenic factors during treatment with sunitinib.
- To explore changes in tumour vascular permeability using dynamic contrast-enhanced MRI (DCE-MRI) in patients receiving sunitinib.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Patients must be ≥ 2 years of age and ≤ 21 years of age at the time of study entry
- Histologically confirmed solid tumor (not required for patients with intrinsic brain stem tumors or optic pathway gliomas). Patients with Recurrent or refractory disease are eligible including primary CNS tumors or known CNS metastases.
- Measurable or evaluable disease
- No known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- Karnofsky performance status (PS) 50-100% (> 10 years of age) OR Lansky PS 50-100% (≤ 10 years of age). Neurological deficits in pts with CNS tumor must have been relatively stable for ≥ 1 week before study enrollment.
- Prior Therapy: Recovered from prior therapy
• At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosoureas).
• At least 1 week since prior and no concurrent hematopoietic growth factors
• At least 1 week since prior antineoplastic biologic agents
• At least 2 weeks since prior local, palliative, small-port radiotherapy (at least 6 months for radiation to ≥ 50% of pelvis). At least 6 weeks since other prior substantial bone marrow radiotherapy
• At least 3 months since prior stem cell transplantation or rescue (without total-body irradiation) and no evidence of graft-vs-host disease
- Organ function requirements:
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³ (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL (transfusions allowed)
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age/gender as follows:
• No greater than 0.8 mg/dL (2 to 5 years of age)
• No greater than 1 mg/dL (6 to 9 years of age)
• No greater than 1.2 mg/dL (10 to 12 years of age)
• No greater than 1.5 mg/dL (male) OR 1.4 mg/dL (female) (13 to 15 years of age)
• No greater than 1.7 mg/dL (male) OR 1.4 mg/dL (female) (≥ 16 years of age)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN
• Albumin ≥ 2 g/dL
• LVEF or shortening fraction normal
• Corrected QT interval ≤ 450 msec
• Amylase ≤ 1.5 times ULN
• Lipase ≤ 1.5 times ULN
• Blood pressure within ULN
|
|
| E.4 | Principal exclusion criteria |
-Prior Therapy:
• No prior anthracycline (any dose)
• No prior radiotherapy to a radiation field that included the heart (including total body or craniospinal irradiation)
• No prior sunitinib malate
- Not Pregnant or nursing women. Fertile patients must use effective contraception
- Concomitant Medications:
• No other concurrent investigational drugs
• No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following: Rifampin, Rifabutin, Carbamazepine, Phenobarbital, Phenytoin, Hypericum perforatum (St. John's wort); Efavirenz; Tipranavir.
• No concurrent antithrombotic or antiplatelet agents, including any of the following: Warfarin, Heparin, Low molecular weight heparin, Acetylsalicylic acid (aspirin), Ibuprofen, Other nonsteroidal anti-inflammatory drugs
• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following: Azole antifungals (e.g., itraconazole or ketoconazole), Clarithromycin, Erythromycin, Diltiazem, Verapamil, HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir), Delavirdine.
- No uncontrolled infection
- No tumors involving the pleural surface
- No pts with body surface area < 0.5 m² (for parts A and B) and < 0.4 m² (for Part C)
- Able to swallow sunitinib malate capsules (parts A and B only)
- No pre-existing thyroid abnormality (hyper- or hypothyroidism) with unstable thyroid function
- No history of allergic reaction attributed to sunitinib malate or component of sunitinib malate capsules
- No patients with known bone marrow metastasis
- No patients with prior allergy to both applesauce and yoghurt (Part C only).
- In pts with primary CNS tumors or known CNS metastases:
• No evidence of new CNS hemorrhage on baseline MRI obtained within 14 days before study enrollment (ECHO gradient MRI sequences per institutional guidelines required for evaluation of CNS hemorrhage)
• The presence of small punctuate CNS hemorrhage on these scans will exclude a patient from participation
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Pharmacokinetics: plasma levels of sunitinib (SU11248) and its main active metabolite (SU12662) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Prior to sunitinib administration and on days 1,7,14, 21, and 28 of cycle 1 and
- in a subset of patients, additionally, 2, 4, 6, and 8-10 hours after sunitinib administration in cycle 1.
- in a subset of patients, additionally, 1,2, 4, 6, 8-10, 24-28, 48-52 hours after sunitinib administration in cycle 1 while not receiving sunitinib on day 2 of cycle 1
|
|
| E.5.2 | Secondary end point(s) |
Activity: disease assessment using imaging studies (with central radiology review)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
During last week of every odd-numbered cycle.
|
|
| 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 | 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 |
| MTD in paediatric patients |
|
| 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 | 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 |
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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
Print
