E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic nasopharyngeal carcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
Cancer in the area behind the nose and above the back of the throat that has come back after receiving standard treatment |
|
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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028793 |
E.1.2 | Term | Nasopharyngeal carcinoma |
E.1.2 | System Organ Class | 100000004864 |
|
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 evaluate the efficacy of CC-486 in patients with nasopharyngeal carcinoma (NPC) |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate safety in all patients
- To evaluate pharmacokinetics of CC-486 in a subset of patients of Asian-Pacific Island ethnicity |
|
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 |
- Pharmacokinetic sample collection in a subset of enrolled patients of Asian-Pacific Island ethnicity
- Biomarker samples collection (stage I of the study as per protocol) |
|
E.3 | Principal inclusion criteria |
- Age = or > 18 years.
- Histological or cytological diagnosis of undifferentiated or poorly differentiated nasopharyngeal carcinoma that is locally advanced or metastatic.
- Disease progression either clinically or radiographically after 1 to 2 previous regimens.
- Patient has received a platinum containing regimen.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- Radiographically-documented measurable disease.
- Adequate organ and bone marrow functions.
- Willingness to follow pregnancy precautions. |
|
E.4 | Principal exclusion criteria |
- History of, or current brain metastasis.
- Any other malignancy within 5 years prior to randomization, with the exception of adequately treated in situ carcinoma of the cervix, uteri, or nonmelanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment), in situ squamous cell carcinoma of the breast, or incidental prostate cancer
- Previous treatment with azacitidine (any formulation), decitabine, or any other hypomethylating agent.
- Impaired ability to swallow oral medication.
- Persistent diarrhea or malabsorption.
- Major surgery within 14 days prior to starting investigational product or has not recovered from major side effects.
- Another investigational therapy within 28 days or 5 half lives of randomization/enrollment, whichever is shorter.
- Patient has not recovered from the acute toxic effects of prior anticancer therapy, radiation, or major surgery/significant trauma.
- Radiotherapy < or = 4 weeks or limited field radiation for palliation < or = 2 weeks prior to starting with the investigational product.
- Any condition that places the patient at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Overall response rate (ORR)
- Progression-free survival (PFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- ORR and PFS: at screening within 28 days before the start of the Investigational Product and after that every 6 weeks (± 5 days) from Cycle 1 Day 1, for the first three tumor evaluations and then every 9 weeks until disease progression or start of a new anticancer treatment, or withdrawal of consent |
|
E.5.2 | Secondary end point(s) |
- Overall survival (OS)
- Safety
- Pharmacokinetics (PK) in a subset of patients of Asian-Pacific Island ethnicity |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- OS: continuously during the trial and every 8 weeks (+/- 5 days) in the Follow-up Period
- Safety: continuously starting after informed consent signature, until 28 days after treatment discontinuation
- PK in a subset of patients of Asian-Pacific Island ethnicity: On each PK day prior to each dose administration and afterwards at 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, and 8h post-dose |
|
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 | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.3 |
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 | 11 |
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 |
Canada |
France |
Greece |
Hong Kong |
Italy |
Romania |
Singapore |
Spain |
Taiwan |
Tunisia |
United States |
|
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
|
Either LVLS or the date of receipt of the last data point from the last patient that is required for primary, secondary, and/or exploratory analysis and/or the Statistical Analysis Plan, 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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |