E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Renal Cell Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
The primary objectives are: - To evaluate median overall survival (OS) from randomization in metastatic renal cell carcinoma (mRCC) patients overall and by subgroup, i.e. in high-risk and in intermediate-risk patients separately, receiving two (2) vaccine doses of Intuvax pre-nephrectomy, followed by sunitinib initiated five (5) to eight (8) weeks post-nephrectomy and in non-vaccinated mRCC patients receiving sunitinib initiated five (5) to eight (8) weeks post-nephrectomy - To evaluate 18-month survival rate from randomization in mRCC patients overall and by subgroup, i.e. in high-risk and in intermediate-risk patients separately, receiving two (2) vaccine doses of Intuvax pre-nephrectomy followed by sunitinib post-nephrectomy and in non-vaccinated patients receiving sunitinib post-nephrectomy |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are (to be evaluated in vaccinated and non-vaccinated patients overall, and in each subgroup (intermediate- and high risk patients) : - To evaluate safety and tolerability - To evaluate PFS according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria from Sunitinib Start Visit - To evaluate response and its duration according to RECIST 1.1 criteria from Sunitinib Start Visit - To evaluate time to progression (TTP) from Sunitinib Start Visit - To evaluate the number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy (sample from either primary tumor or metastasis acceptable) and in the resected primary renal tumor |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Newly (<6 months) diagnosed RCC (histological/cytological verification is optional) with at least one (1) CT-verified metastasis ≥10 mm for which complete metastasectomy is not planned. US patients must have verified clear-cell tumor histology 2) Planned resection of primary tumor 3) Primary tumor diameter ≥40 mm 4) Candidate for first-line therapy with sunitinib initiated five (5) to eight (8) weeks after nephrectomy 5) Female or male ≥18 years of age 6) Willing and able to provide informed consent 7) Adequate hematological parameters, i.e.: • B-Leukocyte count ≥4.5 x109/L • B-Platelet count ≥150 x109/L • B-Hemoglobin (Hb) ≥90 g/L 8) Serum-creatinine and serum-bilirubin ≤1.5 × ULN. Serum-ALAT and serum-ASAT ≤2.5 × ULN (or ≤5 in case of liver metastases) 9) Female who has been post-menopausal for more than one (1) year or female of childbearing potential agreeing to use a highly efficient method of contraception (i.e. a method with less than 1% failure rate [e.g. sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner or combined birth control pills]) from Screening until 90 days after last dose of Intuvax and/or until completed sunitinib treatment whichever occurs later. Female of childbearing potential must have a negative blood pregnancy test at Screening, and if randomized to vaccination a negative blood or urine pregnancy test within one (1) day before each dose of Intuvax) and must not be lactating or Male agreeing to use condoms from Screening until 90 days after last dose of Intuvax and/or until completed sunitinib treatment whichever occurs later, or male having a female partner who is using a highly efficient method of contraception as described above |
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E.4 | Principal exclusion criteria |
1) Life expectancy less than 4 months 2) Central nervous system (CNS) metastasis that is symptomatic or progressing or untreated or that requires current therapy (e.g. evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases) 3) Active autoimmune disease which requires treatment with systemic immunosuppressive agents, e.g. inflammatory bowel disease, multiple sclerosis, sarcoidosis, psoriasis, autoimmune hemolytic anemia, rheumatoid arthritis, SLE, vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other rheumatological diseases 4) Treatment with per oral systemic corticosteroids exceeding 10 mg/day within 7 days before Screening until Nephrectomy (inhaled, intranasal, and local steroids acceptable irrespective of dose) 5) Known cardiomyopathy and/or clinically significant abnormal ECG findings at Screening disqualifying the patient from nephrectomy and subsequent sunitinib treatment 6) Karnofsky performance status <70% For patients in France Karnofsky performance status ≤70% 7) National Cancer Institute (NCI) Common Terminology criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within 28 days before Screening 8) Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication 9) Clinically significant gastrointestinal abnormalities 10) Uncontrolled hypertension, or uncontrolled diabetes mellitus 11) Pulmonary embolism within 12 months prior to Screening 12) Prior history of invasive cancer within 5 years before Screening, except for adequately treated in situ carcinomas or non-melanoma skin cancer 13) Ongoing infection that requires parenteral treatment with antibiotics 14) Active or latent virus disease (HIV, HBV and HCV) 15) ECOG performance status >2 after optimization of analgesics 16) Abnormal or clinically significant coagulation parameters at the discretion of the investigator, i.e.: • Prothrombin Time - International Normalized Ratio (PT-INR) • Activated Partial Thromboplastin Time (APTT) Patients being treated with anticoagulants are excluded if the coagulation parameters are outside the therapeutic intervals as described in the SmPC/USPI for the administered treatment 17) Known major adverse reaction/event in connection with previously made vaccination (e.g. asthma, anaphylaxis or other serious reaction) 18) Known hypersensitivity or allergy to sunitinib or to chemically related products or likely to be exacerbated by any component of the study products 19) Prior systemic antitumor therapy within 28 days before Screening Visit. However, local radiation therapy to any area except for the abdominal/retroperitoneal area including the kidney tumor is allowed 20) Exposure to other investigational products within 28 days prior to Screening Visit 21) Patients on anticoagulants for whom temporarily stop and start, supported by low molecular weight heparin (or other anticoagulation therapy at the discretion of the Investigator and/or per local standard of care) during vaccination and nephrectomy, is not an option 22) History of alcohol or substance abuse 23) Any reason that, in the opinion of the Investigator, contraindicates that the patient participates in the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
- OS from randomization overall in mRCC patients and by each subgroup, i.e. in high-risk and in intermediate-risk mRCC patients - 18-month survival rate from randomization overall in mRCC patients and by each subgroup, i.e. in high-risk and in intermediate-risk mRCC patients |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of study (LVLS or the last subject's safety evaluation [up to 30 days after the last subject's last dose of an IMP], whichever occurs later) |
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E.5.2 | Secondary end point(s) |
- Frequency and proportion of AEs including clinical significant changes in laboratory tests and vital signs from Screening - PFS from start of sunitinib according to RECIST 1.1* - Proportion of Objective Response Rate (ORR) from start of sunitinib treatment and duration of response in each subgroup* - TTP from start of sunitinib treatment* - Relative number of tumor infiltrating CD8+ T-cells in the resected primary tumor compared to relative number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy (sample from either primary tumor or metastasis acceptable)
*Note: For intermediate-risk patients included in the trial according to protocol versions before version Final 4.0, baseline for PFS, ORR and duration of response, and TTP is defined as the first imaging assessment after nephrectomy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study (LVLS or the last subject's safety evaluation [up to 30 days after the last subject's last dose of an IMP], whichever occurs later) |
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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 | 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) | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | No |
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 | 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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LVLS or the last subject's safety evaluation (up to 30 days after the last subject's last dose of an IMP), whichever occurs later |
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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 | 6 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 2 |