E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-line treatment for patients with unresectable, MAGE-A3-positive stage III or stage IVa melanoma |
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MedDRA Classification |
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 |
To evaluate the clinical activity of the recMAGE-A3 + AS15 ASCI in terms of the 1-year overall survival rate (OSR) in patients with MAGE-A3 positive, unresectable stage III or stage IV M1a melanoma presenting with the gene signature identified as being associated with a clinical benefit in response to treatment with the MAGE-A3 + AS15 ASCI
(in the remainder of this document this gene signature is referred to as the predictive gene signature) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the clinical activity of and the immunological response to the recMAGE-A3 + AS15 ASCI in the overall patient population and in the populations of patients presenting with and not presenting with, respectivley, the predictive gene signature. The clinical activity will be assessed in terms of the: •1-year OSR in the overall patient population and in patients not presenting the predictive gene signature; • progression-free survival (PFS); • 6-month and 1-year progression-free survival rate (PFSR); • median overall survival (OS); • Time to Treatment Failure (TTF); • overall clinical response rate and the duration of response; • The humoral and cellular immune response will be assessed in terms of the immunological response rate; • To assess the safety of the recMAGE-A3 + AS15 ASCI in the overall population. • To examine the correlation between test results obtained on fresh tumor tissue and on FFPE tissue
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients with histologically proven metastatic cutaneous melanoma that is measurable. 2. Patients with regional or distant cutaneous, subcutaneous or lymph-node metastasis can be included in the study, provided the disease is not amenable to curative treatment with surgery. In terms of the AJCC 2002 classification, this includes patients with unresectable stage III melanoma including in-transit metastases or patient with stage IV M1a melanoma. 3. Written informed consent obtained from the patient prior to performance of any study specific procedure. 4. Patient is at least 18 years old at the time of signature of the informed consent form. 5. The patient’s tumor expresses MAGE-A3, as determined by RT-PCR analysis on a fresh tumor tissue sample obtained during the screening phase. 6. Fresh tissue from the same lesion must be available for MAGE-A3 expression testing and for the testing of the predictive gene signature. 7. Formalin-fixed paraffin-embedded (FFPE) tissue must be available for complementary MAGE-A3 and gene signature testing. This FFPE tissue should preferably come from the same (reference) lesion as the fresh tissue used for MAGE-A3 and gene signature testing but may be taken from a second lesion during the screening phase if the reference lesion does not provide sufficient tissue. 8. Patient fully recovered from any previous intervention (i.e., biopsy). 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 10. Adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria. 11. If the patient is female, she must be of non-childbearing potential, i.e., have a current tubal ligation, hysterectomy, ovariectomy or be post menopausal, or if she is of childbearing potential, she must practice adequate contraception for at least 30 days prior to registration in the trial, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the injection series. 12. In the opinion of the investigator, the patient can and will comply with the protocol requirements.
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E.4 | Principal exclusion criteria |
1. Patients with unresectable stage IV M1b,c melanoma and patients with ocular and mucosal melanoma. 2. The patient has at any time received any systemic anticancer treatment. • Prior systemic treatment with an immunomodulator (i.e., interferon or/and anti-CTL-A4 therapy) or loco-regional radiotherapy is permitted as prior adjuvant treatment provided that the last dose was administered at least 30 days before the registration into this trial; • Previous adjuvant treatment with a cancer vaccine containing a tumor antigen other than MAGE-A3 is allowed if the last administration took place at least 8 weeks before registration into the trial. • Prior isolated limb perfusion is permitted provided that the last dose was administered at least 30 days before registration into this trial. 3. The patient is scheduled to receive any anti-cancer specific treatment, including radiotherapy, other immunotherapy, chemotherapy and immunomodulating agents. 4. The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids, or any other immunosuppressive agents. The use of prednisone, or equivalent, at a dose of no more than 0.125 mg/kg/day (absolute maximum 10 mg/day) or topical steroids is permitted. 5. The patient has a history of autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded. 6. The patient has a family history of congenital or hereditary immunodeficiency. 7. The patient is known to be positive for Human Immunodeficiency Virus (HIV). 8. History of allergic disease or reactions likely to be exacerbated by any component of the ASCI treatment. 9. The patient has previous or concomitant malignancies at other sites, except • Effectively treated non-melanoma skin cancer or carcinoma in situ of the cervix • Effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured. 10. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures. 11. The patient has an uncontrolled bleeding disorder. 12. The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk. 13. Use of any investigational or non-registered product (drug or vaccine) other than the study medication within the 30 days preceding the first dose of study treatment or planned use during the study period. 14. Concurrently participating in another clinical study, at any time during the study period, in which the patient has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). 15. For female patients: the patient is pregnant or lactating.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be survival status 1 year after study entry. Secondary endpoints include: • Progression-free survival (PFS) defined as the time from the date of registration of the patient to either the date of disease progression or the date of death (for whatever reason), whichever comes first. Patients alive and without disease progression are censored at the date of the last visit/contact; • The progression status at 6 months (Week 23) and 1 year (Week 53) after study entry; • Overall survival (OS) defined as the time from registration of the patient until death. Patients alive at the time of analysis are censored at the time of the last visit/contact; • Time to Treatment Failure (TTF) defined as the time from registration of the patient until the date of the last treatment administration, irrespective of the reason for study treatment discontinuation. • Best clinical response; • The duration of response for patients with CR, PR or SD status. • Anti-MAGE-A3, anti-protein D and anti-CpG titres at the different collection time points; • Anti-MAGE-A3, anti-protein D and anti-CpG seropositivity at the different collection time points; • Anti-MAGE-A3, anti-protein D and anti-CpG seroconversion at the different collection time points; • The MAGE-A3 cellular (T-cell) response (a T-cell responder is defined as a patient with an increased amount of antigen-specific T-cells after immunization as compared to the baseline value). These specific T-cells include the CD4+ or CD8+ T-cells producing cytokines and/or presenting cytolytic activity, and/or specific CD4+ or CD8+ T-cells presenting a particular phenotype (effector/memory)). • Occurrence of adverse events up to 30 days after each study dose injection, including abnormal values of haematological and biochemical variables • Occurrence of serious adverse events and autoimmunity during the whole duration of the study (up to 30 days after the last administration of the study treatment). • The correlation between test results obtained on fresh tumor tissue and on FFPE tissue. |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 1 |
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 | Information not present in EudraCT |
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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Last visit of the last patient taking part in 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 | 5 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |