E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HLA-A*02-positive patients with advanced clear cell RCC who have progressed during or after first-line systemic therapy for advanced disease and have a favourable or intermediate risk after systemic therapy according to the 3-score risk cc prognostic risk category (Metzer 2004). |
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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 | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
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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 2 study is to determine whether IMA901 as single agent with GM-CSF as adjuvant shows sufficient anti-tumor efficacy in patients with advanced RCC to warrant further development. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are safety, immunological parameters, the potential of low-dose cyclophosphamide (CY) to improve immune response to IMA901, and additional efficacy endpoints. |
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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 3. Histologically documented advanced clear-cell RCC 4. Patients must have received first-line tyrosine kinase inhibitor or cytokine systemic therapy for advanced disease and must be candidates for second-line therapy. * 5. Patients having experienced documented tumor progression during or after first-line systemic therapy. Documentation of progression must be either imaging based (i.e. any increase in lesion size and/or an increase in the number of tumor lesions) or based on clinical (symptomatic) tumor progression. 6. At least one unidimensional measurable target lesion documented by adequate imaging and assessable according to the RECIST criteria, whereby target lesions must not lie in a previously irradiated area 7. Karnofsky Performance Status lower than 80 8. Favorable or intermediate risk according to the 3-score MSKCC criteria (see Section 4.5.3 of the protocol). The subject has a favorable risk if none, or intermediate risk if only one of the following criteria applies (if two or three criteria apply the subject is not eligible): a. Karnofsky performance status lower than 80 b. Serum haemoglobin ≤ 13 g/dL for males and ≤ 11.5 g/dL for females c. Corrected serum calcium ≥ 10 mg/dL 9. Able to understand the nature of the study and give written informed consent 10. Willingness and ability to comply with the study protocol for the duration of the study *NOTE: in Germany only patients after first-line tyrosine kinase inhibitor failure will be included into the study as per amendment no. 1 |
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E.4 | Principal exclusion criteria |
1) Poor risk according to the 3-score MSKCC criteria (see Section 4.5.3 of the protocol). 2) Immunosuppressive therapy within 4 weeks before Visit C, e.g. corticosteroid treatment (exceptions are corticosteroid substitution therapy for adrenal insufficiency or inhalative corticosteroids for e.g. asthma) 3) History of other malignant tumors, except non-melanoma-skin cancer or curatively excised cervical carcinoma in situ 4) Presence of brain metastases on MRI or CT scan 5) Patients with a history or evidence of systemic autoimmune disease 6) Any vaccination in the two weeks before Visit C 7) Any planned prophylactic vaccination from study entry until the end of the induction period (5 weeks after the first vaccination) 8) Known active hepatitis B or C infection 9) Known HIV infection 10) Any other 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 tuberculosis, coccidiodes immitis. 11) Any of the following in the 4 weeks before Visit C: a) Major surgery b) Anticancer treatments including (but not limited to) cytotoxic chemotherapy, radiotherapy, immunotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies c) Unresolved toxicity from prior anticancer treatments including (but not limited to) cytotoxic chemotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies, radiotherapy, or immunotherapy d) Received study drug within any clinical study (including approved and experimental drugs) 12) Any of the following abnormal laboratory values: a) Hematology: Hb < 10 g/dL; WBC < 3 x 10^9/L; neutrophils < 1.5 x 10^9/L; lymphocytes < 1.5 x 10^9/L; platelets < 100 x 10^9/L b) Liver function: serum bilirubin > 1.5 x upper normal limit (unless a history of Gilbert’s disease); ALAT or ASAT > 3 x upper normal limit (>5 x upper normal limit if liver metastases are present) c) Renal function: serum creatinine > 200 µmol/L 13) Patients with other significant diseases currently uncontrolled by treatment which might interfere with study completion, including gastrointestinal, hepatic, renal, respiratory, cardiovascular, hematological, coagulation, metabolic or hormonal diseases with clinically relevant abnormal organ function for example: a) Heart failure or non compensated active heart disease (≥ New York Heart Association III, see Appendix 2 of the protocol) b) Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension c) Symptomatic neurotoxicity (motor or sensory) ≥ grade 2 National Cancer Institute – Common Toxicity Criteria (NCI-CTC).d) Severe pulmonary dysfunction 14) Psychiatric disabilities, seizures or central nervous system disorders that may interfere with the ability to give informed consent or perform adequate follow-up in the investigator’s opinion 15) Active infections requiring oral or intravenous antibiotics 16) Women or men who decline to practice a medically approved method of contraception 17) Pregnancy or breastfeeding 18) Any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study (e.g. poor medical risks because of non malignant disease, or secondary effects of cancer) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is defined as the DCR at Visit 14 (after 26 weeks of treatment) as compared to baseline. This endpoint represents a composite of the objective response rate (ORR) and stable disease (SD) rate, where ORR is defined as the complete response (CR) rate plus partial response (PR) rate. All deaths regardless of cause will be considered as events for the assessment of DCR. The assessment of the primary endpoint will be based on RECIST with the modification that baseline assessments will be used as the only reference point (intermediate tumor assessments will not be taken into account). |
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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 |
in a subpopulation analysis of tumor tissue (RNA, peptids etc) |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
randomisation only affects secondary endpoint (cyclophosphamide) |
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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 |
pre-treatment with cyclophosphamide for 1 treatment arm |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 68 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |