| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent or progressive primary brain tumors in one of four primary brain tumor types: high-grade glioma, medulloblastoma, ependymoma and diffuse intrinsic pontine glioma (DIPG |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 |
| To identify potential tumor type(s) for further development by establishing the preliminary efficacy of pomalidomide in children and young adults with recurrent or progressive primary brain tumors within four distinct tumor types. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the safety of pomalidomide within the study populations.
To estimate the long-term efficacy of pomalidomide treatment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is 1 to < 21 years of age at the time of signing the ICF/IAF.
2. Subject must understand and voluntarily sign an ICF/IAF prior to any study-related assessments/procedures being conducted.
3. Subject has received at least one prior standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy.
4. Subject has a diagnosis of high-grade glioma, medulloblastoma, ependymoma or DIPG that is recurrent or progressive.
5. Subject has histological verification of tumor either at the time of diagnosis or recurrence.
6. Subject has measurable disease, defined as a tumor that is measurable in two perpendicular diameters on MRI.
7. To document the degree of tumor through scan;
8. Subject has Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening (Appendix D)
9. Subject has adequate bone marrow function;
10. Subject has adequate renal function;
11. Subject has adequate liver function;
12. Subject has adequate pulmonary function;
13. Subject has recovered from clinically significant acute treatment related toxicities from all prior therapies.
14. Subject has no significant worsening in clinical status for a minimum of 7 days prior to first dose of study drug;
15. Subject (and when applicable, with parental/legal representative) is willing and able to adhere to the study visit schedule and other protocol requirements.
16. Females of Childbearing Potential (FCBP), Female Children of Childbearing Potential (FCCBP), and male subjects who have reached puberty (and when applicable, with parental/legal representative) must agree to undergo physician-approved reproductive education and discuss the side effects of the study therapy on reproduction.
17. All subjects and/or parents/legal representative must have an understanding that pomalidomide could have a potential teratogenic risk. Female children of childbearing potential, defined as females who have achieved menarche and/or breast development in Tanner Stage 2 or greater and have not undergone a hysterectomy or bilateral oophorectomy and FCBP, defined as a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) must agree and meet the following conditions below:
-Medically supervised pregnancy tests with a sensitivity of at least 25 mIU/mL must be conducted in FCCBP/FCBP, including those who commit to true abstinence*.
Two pregnancy tests must be conducted prior to starting pomalidomide. The first pregnancy test must be performed 10 to 14 days prior to the start of pomalidomide and the second pregnancy test must be performed within 24 hours prior to starting pomalidomide. The subject may not receive pomalidomide until the Investigator has verified that the results of these pregnancy tests performed on Cycle 1, Day 1 are negative. Female children of childbearing potential/females of childbearing potential with regular or no menstrual cycles must agree to have pregnancy tests weekly for the first 28 days study participation, every 28 days while on study, at study treatment discontinuation visit, and at Day 28 following pomalidomide discontinuation. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days of study participation and then every 14 days while on study, at study treatment discontinuation visit, and at Days 14 and 28 following pomalidomide discontinuation.
-Female subjects must, as appropriate to age and at the discretion of the study Investigator, either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis) and/or agree to the use of two reliable forms of approved and effective contraceptive methods simultaneously. The two methods of reliable contraception must include one highly effective method (ie, oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; vasectomized partner) and one additional effective barrier method (ie, male condom, diaphragm, cervical cap) 28 days prior to starting pomalidomide, throughout the entire duration of study treatment including dose interruptions and 28 days after discontinuation of pomalidomide.
-All male and female subjects must follow all requirements defined in the pomalidomide Pregnancy Prevention Program.
18. Male subjects must, as appropriate to age and the discretion of the study physician:
-Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions and for at least 28 days following pomalidomide discontinuation, even if he has undergone a successful vasectomy or practices complete abstinence. |
|
| E.4 | Principal exclusion criteria |
1. Subject has a history of non-central line related thrombosis (arterial or venous), more than one prior central-line related thrombosis or known coagulopathy.
2. Subject has first degree family member with a known hereditary coagulopathy.
3. Subject is actively on anticoagulation therapy.
4. Subject has had major (per Investigator discretion) surgery, with the exception of tumor resection, within 21 days from first dose of study drug.
5. Subject has previously received (presence of any of the following will exclude a subject from enrollment):
-Any prior treatment with pomalidomide. Subjects who have prior treatment with other IMiDs (thalidomide, lenalidomide) ARE eligible if they meet all other eligibility criteria and did not have allergic reactions or other “significant toxicity” per Investigator discretion associated with lenalidomide or thalidomide use.
-Myelosuppressive chemotherapy, immunotherapy, or any investigational agent: ≤ 28 days (≤ 42 days if a nitrosourea) prior to screening.
-Biological (anti-neoplastic) therapy: ≤ 7 days prior to screening.
-Immunomodulatory therapy: ≤ 28 days prior to screening.
-Monoclonal antibody treatment and agents with known prolonged half-lives: < 3 half-lives have elapsed or ≤ 28 days prior to screening, whichever is longer.
-Prior radiation:
.Cranial irradiation, total body irradiation (TBI), or ≥ 50% radiation of pelvis: ≤ 3 months prior to screening.
.Focal irradiation: ≤ 6 weeks prior to screening.
.Local palliative radiation therapy (small port): < 4 weeks prior to screening.
-Bone marrow transplant:
.Presence of graft versus host disease (GVHD)
. < 6 months since allogeneic bone marrow transplant prior to screening.
. < 3 months since autologous bone marrow/stem cell transplant prior to screening.
. < 3 months since stem cell transplant (SCT) or Rescue without TBI with no evidence of GVHD prior to screening.
- Radioisotopes: fluorothymidine (18FLT) ≤ 72 hours prior to first dose of study drug
8. Subject is pregnant, breast-feeding or lactating. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Objective response and long-term stable disease rate |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Cycle 1, Day 1 to completion of Cycle 6 (completion of Cycle 3 for DIPG) |
|
| E.5.2 | Secondary end point(s) |
1. Objective response rate
2. Long-term stable disease rate
3. Duration of response
4. Progression-free survival
5. Overall Survival
6. Safety |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Cycle 1, Day 1 of Treatment Period to end of Follow-up Period
2. Cycle 1, Day 1 to completion of Cycle 6 (completion of Cycle 3 for DIPG)
3. Cycle 1, Day 1 of Treatment Period to end of Follow-up Period
4. Cycle 1, Day 1 of Treatment Period to end of Follow-up Period
5. Cycle 1, Day 1 of Treatment Period to end of Follow-up Period
6. Signing of informed consent form (ICF)/informed assent form (IAF) until the end of Follow-up Period |
|
| 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 | 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 | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 |
| France |
| Italy |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
| The End of Trial is defined as either the date of the last visit of the last subject to complete the post-treatment follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 28 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 28 |
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