E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castration-Refractory Prostate Cancer |
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E.1.1.1 | Medical condition in easily understood language |
prostate cancer that has spread to other organs and no longer responds to standard hormonal therapy |
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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 | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The primary objective of this study is to compare treatment Arm A (IMC-3G3 plus mitoxantrone plus prednisone) and Arm B (mitoxantrone plus prednisone) in terms of progression-free survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to:
- Compare the overall survival (OS) of both arms
- Compare the objective response rate (ORR), according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1) of both arms
- Evaluate the prostate-specific antigen (PSA) doubling time in both arms and evaluate the PSA response rate according to two definitions: 1) response manifested by a 50% decline in pretreatment PSA and 2) response defined by a 30% decline in pretreatment PSA at 12 weeks
- Assess the safety and tolerability of IMC-3G3 (with prednisone) with and without mitoxantrone
- Explore circulating tumor cells (CTC) in whole blood and PDGFRα expression, and their associations with efficacy endpoints
- Examine the pharmacokinetics (PK) of IMC-3G3 in combination with mitoxantrone and prednisone and immunogenicity of IMC-3G3. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically-confirmed adenocarcinoma of the prostate
- castration resistant
- progression after or toxicity of docetaxel
- adequate hematologic, hepatic and renal function
- life expectancy > 3 months
- the patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing
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E.4 | Principal exclusion criteria |
- more than 1 cytotoxic chemotherapy regimen for metastatic disease
- prior therapy with mitoxantrone for prostate cancer
- history of prior treatment with agents directly inhibiting PDGF[R]
- radiotherapy ≤ 21 days prior to first dose of IMC-3G3
- any investigational therapy within 30 days of randomization
- prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radio nucleotide therapy and has either ongoing evidence of bone marrow dysfunction or bone pain that is poorly controlled in the opinion of the investigator
- ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, psychiatric illness, active bleeding, other serious uncontrolled medical disorders
- known or suspected brain or leptomeningeal metastases
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-Free Survival (see section 12.5 for details).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
include OS/ORR/PSA/PGDFR-alpha/cmax/antibody assessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
patient-reported outcomes, exploratory, biomarker analyses |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
arm B patients can transfer to 3G3+prednisone after progression of disease |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | No |
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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This study will be considered discontinued when the trial has been terminated by ImClone or when all of the
following criteria are met:
- No patient continues to receive study therapy;
- All patients have completed the 30-day follow-up evaluation subsequent to last dose;
- A sufficient number of PFS events have occurred to perform the primary analysis; and
- ≥ 75% of OS events have occurred. |
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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 |