E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Platinum-refractory and platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033131 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016180 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052171 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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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 |
To estimate the objective antitumor response rate of MLN8237 using the Response Evaluation Criteria in Solid tumors (RECIST criteria) or CA 125 criteria in patients with platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. |
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E.2.2 | Secondary objectives of the trial |
To estimate the progression-free survival (PFS), duration of response (DOR), time to disease progression (TTP), and the clinical benefit (response and stable disease [SD]) associated with MLN8237.
To further characterize the adverse event (AE) profile associated with MLN8237. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each patient must meet all of the following inclusion criteria to be enrolled in the study:
1. Female patients 18 years or older
2. Patients must have a diagnosis of histologically or cytologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR • Are surgically sterile, OR • If they are of childbearing potential, agree to practice 2 effective methods of nonhormonal contraception, at the same time, from the time of signing the informed consent form (ICF) through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
5. The patient or the patient’s legal representative is able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
6. Clinical laboratory values as specified below within 7 days before study entry:
• Absolute neutrophil count (ANC) ≥ 1,500/μL • Platelet count ≥100,000/ μL • Total bilirubin must be less than 1.5 times the upper limit of the normal range (ULN) • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be ≤ 2.5 times the ULN. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of metastatic disease in liver. • Creatinine clearance as calculated by the method of Cockroft and Gault ≥ 30 mL/minute.
7. Platinum-refractory malignant disease or platinum-resistant malignant disease:
• Platinum-refractory malignant disease, characterized by a lack of response, progression, or recurrence of malignant disease during treatment with a platinum-based treatment regimen; OR • Platinum-resistant malignant disease, characterized by progression or recurrence of malignant disease within 6 months after the last dose of platinum on a platinum-based treatment regimen
8. Measurable neoplastic disease according to the RECIST criteria, ie, 1 or more lesions that can be accurately measured in at least 1 dimension (longest dimension to be recorded) and at least 2 cm by conventional techniques or at least 1 cm by spiral CT scan and at least 1 target lesion to assess response. Tumors within a previously irradiated field are considered nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence of malignancy 90 days or more following completion of radiotherapy.
OR
A CA 125 level of > 40 units/mL AND clinical evidence of neoplastic disease (eg, ascites, pleural effusion, peritoneal implantation, etc). Patients who simply have an elevated CA 125 level without clinical evidence of neoplastic disease are NOT eligible for the study.
9. Recovered (ie, ≤ Grade 1 toxicity or patient’s baseline status) from the reversible effects of prior antineoplastic therapy |
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E.4 | Principal exclusion criteria |
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
1. Pregnant or lactating
2. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol
3. Treatment with any investigational products within 28 days before the first dose of study drug
4. Receipt of more than 4 regimens of prior systemic therapy, 2 of which may be platinum-based cytotoxic chemotherapy, 1 of which may be a nonplatinum cytotoxic regimen, and 1 biological therapy NOT part of a cytotoxic regimen
5. Known CNS metastases
6. Prior allogeneic bone marrow or organ transplantation
7. Radiotherapy within 21 days preceding the first dose of study drug
8. Radiotherapy to more than 25% of the hematopoietically active bone marrow
9. Major surgery within 14 days preceding the first dose of study drug
10. Infection requiring systemic antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection
11. Inability to swallow orally administered medication
12. Diagnosis or treatment of another malignancy within 2 years preceding the first dose of study drug except for nonmelanoma skin cancer that has been completely resected, or any in situ malignancy that has been completely resected
13. Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Combined objective response rate, defined as CR+PR by RECIST criteria or response by CA 125 criteria. |
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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 | 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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | Information not present in EudraCT |
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 |
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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.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |