E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study population consists of HLA-A*02-positive metastatic and/or locally advanced RCC patients with histology of the clear-cell type who are aged 18 years or older and have a favorable or intermediate risk according to the 6-score Heng criteria (Heng et al, 2009). Patients must be planned to receive standard first-line therapy with sunitinib irrespective of their participation in the trial. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038415 |
E.1.2 | Term | Renal cell carcinoma stage unspecified |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the present phase III study is to investigate whether IMA901 can prolong overall survival in patients with metastatic and/or locally advanced renal cell carcinoma (RCC) when added to standard first-line therapy with sunitinib |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include a subgroup analysis of overall survival in patients who are positive for a prospectively defined primary biomarker signature, the investigation of progression-free survival, best tumour response, safety and immunological parameters (in a subset of patients). Further objectives are additional biomarker analyses. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged at least 18 years 2. HLA type: HLA-A*02-positive (assessed by a central laboratory, the result of HLA-testing will be available within a maximum of 5 days) 3. Metastatic and/or locally advanced RCC with clear cell histology (histological confirmation by local pathologist required). NOTE: prior nephrectomy is NOT required. 4. Measurable and/or non-measurable tumor lesions as per RECIST 1.1 based on the local assessment. 5. Patients who are candidates for a first-line therapy with sunitinib 6. Favorable or intermediate risk according to the 6-score risk criteria in patients treated with VEGF-targeted agents according to Heng (Heng et al, 2009). Laboratory values for risk categorization will be determined by a central laboratory. The subject has a favorable risk if none, or intermediate risk if one or two of the following criteria apply (if three or more criteria apply the subject is not eligible): a. Hemoglobin < LLN b. Serum corrected calcium > ULN c. Karnofsky performance status < 80% d. Time from initial diagnosis to initiation of therapy < 1 year e. Absolute neutrophil count > ULN f. Platelets > ULN 7. Able to understand the nature of the study and give written informed consent 8. Willingness and ability to comply with the study protocol for the duration of the study 9. Female patients who are post menopausal (no menstrual period for a minimum of 1 year), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or practice one of the following medically acceptable methods of birth control: • Hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the patient’s usual menstrual cycle period) before study entry. • Intrauterine device (IUD). • Double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream). 10. Male patients willing to use contraception (condoms with spermicidal jellies or cream) upon study entry and during the course of the study or have undergone vasectomy |
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E.4 | Principal exclusion criteria |
1. Prior systemic therapy for metastatic disease. (Note: prior adjuvant treatment for non-metastatic disease is allowed, however adjuvant therapy must have been stopped ≥ 1 year before Visit C). 2. History of or current brain metastases. 3. Abnormal ≥ CTC Grade 3 laboratory values at screening 2 (assessed by a central laboratory) for hematology (Hb, WBC, neutrophils, lymphocytes, platelets), liver (serum bilirubin, ALAT or ASAT) and renal function (serum creatinine). 4. Metastatic second malignancy 5. Localized second malignancy expected to influence the patient’s life span. 6. Patients with a history or evidence of systemic autoimmune disease, e.g. rheumatoid arthritis, multiple sclerosis, systemic lupus erythematodes (SLE), scleroderma, Sjögren's syndrome, Wegener's granulomatosis, Guillain-Barre syndrome 7. Known active hepatitis B or C infection 8. Known HIV infection 9. Active infections requiring oral or intravenous antibiotics 10. Any other known infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patient tissues. Examples are: rabies, mycobacterium leprae, plasmodium falciparum, coccidiodes immitis. 11. Received study drug within any clinical study (including approved and experimental drugs) within 4 weeks before sunitinib start 12. Serious intercurrent illness, which according to the investigator, poses an undue risk for the patient when participating in the trial, including, but not limited to, any of the following: • Clinically significant cardiovascular disease (e.g., uncontrolled hypertension; clinically significant cardiac arrhythmia, clinically significant QT-prolongation), • New York Heart Association class III-IV congestive heart failure • Symptomatic peripheral vascular disease • Severe pulmonary dysfunction • Psychiatric illness or social situation that would preclude study compliance 13. Less than 12 months since any of the following: • Myocardial infarction • Severe or unstable angina • Coronary or peripheral artery bypass graft • Cerebrovascular event incl. transient ischemic attack • Pulmonary embolism / deep vein thrombosis (DVT) 14. Pregnancy or breastfeeding 15. Any condition which in the judgment of the investigator would place the patient at undue risk or interfere with the results of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS), comparing patients receiving or not vaccination therapy with IMA901 in addition to first-line therapy with sunitinib. The main analysis will test the primary endpoint defined as time from randomisation until death of any cause. A sensitivity analysis will test the primary endpoint defined as time from start of sunitinib treatment until death of any cause. |
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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 |
Cellular immunomonitoring in a subset of patients |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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 |
standard first-line therapy with sunitinib without IMA901 |
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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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
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 | 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 study will be completed when all patients had the chance to complete V14. The final data cut-off for overall survival analysis is estimated to be 27 months after the date of randomisation of the last patient; data collected up to that point wil be included in the clinical study report. |
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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 | 3 |
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 | 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 |