E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001388 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001388 |
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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 |
The primary objective of this study is to determine the overall survival (OS) of single agent OSI-906 (Arm A) versus placebo (Arm B) in patients with adrenocortical carcinoma (ACC) who received at least 1 but no more than 2 prior drug regimens. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate: progression-free survival (PFS), disease control rate (DCR), best overall response rate (ORR), and duration of response; quality of life (as measured by EORTC QLQ-C30); the safety profile of OSI-906; the pharmacokinetic profile of OSI-906; and pharmacodynamic changes and correlations with treatment outcome. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: 1. Histologically confirmed adrenocortical carcinoma that is locally advanced or metastatic and not amenable to surgical resection. 2. Measurable disease according to RECIST (version 1.1). 3. Radiologically-confirmed progressive disease within 6 months prior to randomization. 4. Age 18 years. 5. ECOG PS 2. 6. Predicted life expectancy 12 weeks. 7. At least 1 but no more than 2 prior drug regimens (including molecular targeted therapy, systemic cytotoxic chemotherapy, biologics, and/or vaccines) for locally advanced/metastatic ACC. A minimum of 3 weeks must have elapsed between the end of prior treatment and randomization. a. All patients must have received prior mitotane, either as neoadjuvant, adjuvant, or locally advanced/metastatic therapy. b. Adjuvant and neoadjuvant mitotane therapy will not be counted as prior drug regimens or as systemic cytotoxic chemotherapy. 8. Prior radiation therapy is permitted provided patients have recovered from the acute, toxic effects of radiotherapy prior to randomization. A minimum of 21 days must have elapsed between the end of radiotherapy and randomization. 9. Prior surgery is permitted provided that adequate wound healing has occurred prior to randomization. 10. Fasting glucose 150 mg/dL (8.3 mmol/L). Concurrent use of non-insulinotropic oral antihyperglycemic therapy is permitted if the dose has been stable for 4 weeks at the time of randomization. 11. Adequate hematopoietic, hepatic, and renal function defined as follows: Neutrophil count 1.5 x 109/L; Platelet count 100 x 109/L; AST and ALT 2.5 x ULN, or 5 x ULN if patient has documented liver metastases or received prior mitotane therapy; and Serum creatinine 1.5 x ULN or ≤ 2.0 x ULN if the patient has received prior cisplatin. 12. Patients � both males and females � with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must agree to practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to randomization. 13. Patients must provide verbal and written informed consent to participate in the study. |
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E.4 | Principal exclusion criteria |
Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or insulin therapy. 2. Prior IGF-1R inhibitor therapy. 3. History of prior malignancy, except for resected basal cell or squamous cell carcinoma of the skin, cured in situ cervical carcinoma, cured ductal carcinoma in situ of the breast, or other cancers where the patient has been disease-free for 3 years. 4. History of significant cardiovascular disease unless the disease is well-controlled. Significant cardiac diseases includes second/third degree heart block; clinically significant ischemic heart disease; QTcF interval > 450 msec at screening; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea). 5. History of cerebrovascular accident (CVA) within 6 months prior to randomization or that resulted in ongoing neurologic instability. 6. Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing. 7. Active infection or serious underlying medical condition (including any type of active seizure disorder within 12 months prior to randomization) that would impair the ability of the patient to receive study drug. 8. History of any psychiatric condition that might impair the patient�s ability to understand or to comply with the requirements of the study or to provide informed consent. 9. Pregnant or breast-feeding females. 10. Symptomatic brain metastases that are not stable, require steroids, are potentially life-threatening, or that have required radiation within 28 days prior to randomization. 11. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
All randomized patients will be included in the efficacy analyses of OS. Following the intent-to-treat principle, patients will be analyzed according to the treatment they were assigned to at randomization. The primary efficacy variable is OS. The secondary efficacy variables include PFS, DCR, best ORR, duration of response and time to deterioration in quality of life (as measured by EORTC QLQ-C30). |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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The end of the study will be approximately 1 month after the date when at least 112 OS events have occurred in patients participating in this clinical 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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |