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 high-risk metastatic renal cell carcinoma (mRCC) patients receiving two (2) vaccine doses of Intuvax (10x10^6 dendritic cells [DCs]) pre-nephrectomy, followed by Sunitinib initiated five (5) to eight (8) weeks post nephrectomy and in non-vaccinated high-risk mRCC patients receiving Sunitinib initiated five (5) to eight (8) weeks post-nephrectomy.
- To evaluate 18 months survival rate from randomization in intermediate-risk mRCC patients receiving two (2) vaccine doses of Intuvax (10x10^6 DCs) pre-nephrectomy followed by Sunitinib post-nephrectomy and in non-vaccinated intermediate-risk patients receiving Sunitinib post-nephrectomy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate
- safety and tolerability in high and intermediate-risk mRCC patients given 2 doses of Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy and in non-vaccinated patients given Sunitinib post-nephrectomy
- PFS according to RECIST 1.1 criteria from Sunitinib Start Visit in intermediate-risk and high-risk mRCC patients after given 2 doses of Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy and in non-vaccinated patients given Sunitinib post-nephrectomy
- response according to RECIST 1.1 criteria (12 weeks from Sunitinib Start Visit) in intermediate and high-risk mRCC patients given 2 doses of Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy and in non-vaccinated patients given Sunitinib post-nephrectomy
- the number of infiltrating CD8+ T-cells in the resected primary renal tumor in intermediate and high-risk mRCC patients given 2 doses of Intuvax pre-nephrectomy and in non-vaccinated patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Recent (<6 months) diagnosed RCC with at least one (1) CT-verified metastasis
- Planned resection of primary tumor
- Primary tumor diameter ≥4 cm
- Candidate for standard first-line therapy with Sunitinib
- Female or male ≥18 years of age
- Willing and able to provide informed consent
- Adequate hematological parameters, i.e:
B-Leukocyte count ≥4.5 x10^9/L
B-Platelet count ≥150 x10^9/L
B-Haemoglobin ≥100 g/L
- Adequate liver function, i.e. Child-Pugh maximum stage A
- Female who has been post-menopausal for more than one (1) year or female of childbearing potential using a highly efficient method of contraception (i.e. a method with less than 1% failure rate [e.g. sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner or combined birth control pills]) during the study. 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 during the study, 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 |
- Life expectancy less than 4 months
- 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
- Treatment with systemic corticosteroids (inhaled, intranasal and local steroids accepted) within 7 days before Screening.
- Known cardiomyopathy and/or clinical significant finding in ECG at Screening
- Karnofsky performance status <70%, Section 3.2
- NCI CTCAE Grade 3 hemorrhage within 28 days before Screening
- Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
- Clinically significant gastrointestinal abnormalities
- Uncontrolled hypertension, or uncontrolled diabetes mellitus
- Pulmonary embolism within 12 months from randomization
- Prior history of invasive malignancy, except for adequately treated in situ carcinomas or non-melanoma skin cancer
- Ongoing infection that requires parenteral treatment with antibiotics
- Active or latent virus disease (HIV, HBV and HCV)
- ECOG performance status >2 after optimization of analgesics, Section 3.2
- Inadequate coagulation parameters, i.e:
* Prothrombin Time - International Normalized Ratio (PT-INR)
* Activated Partial Thromboplastin Time (APTT)
- Known major adverse reaction/event in connection with previously made vaccination (e.g. asthma, anaphylaxis or other serious reaction)
- Known hypersensitivity or allergy to Intuvax, to chemically related products
- Prior antitumor therapy within 28 days before Screening visit
- Exposure to other investigational products within 28 days prior to Screening
- History of alcohol or substance abuse
- 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) |
- Median OS after randomization in high-risk mRCC patients from the two (2) treatment arms
- 18 months survival rate after randomization in intermediate-risk mRCC patients from the two (2) treatment arms |
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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) |
- Characterization of AEs (frequency and severity) including clinical significant changes in laboratory tests, Child-Pugh score, and vital signs from Screening from the two (2) treatment arms
- PFS from Screening visit in intermediate-risk mRCC patients according to RECIST 1.1, in the two (2) treatment arms
- PFS from Sunitinib Start Visit in intermediate-risk mRCC patients according to RECIST 1.1, in the two (2) treatment arms
- PFS from Sunitinib Start Visit in high-risk mRCC patients according to RECIST 1.1, in the two (2) treatment arms
- Number of patients with CR, PR, PD, SD, and 'Not Evaluable' (within 12 weeks from Sunitinib Start Visit) in intermediate- and high-risk mRCC patients from the two (2) treatment arms
- Number of tumor infiltrating CD8+ T-cells in the resected primary tumor in the two (2) treatment arms |
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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 | 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
| 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 | 20 |
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 | 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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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 | 2 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 2 |