Intratumoral Vaccination With Intuvax Pre-nephrectomy Followed by Sunitinib Post-nephrectomy vs Sunitinib Post-nephrectomy in Newly Diagnosed Metastatic Renal Cell Carcinoma (mRCC)
Condition: Renal Cell Carcinoma, Metastatic
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Intuvax (INN: ilixadencel); Sunitinib
Intervention description: Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.; Cytostatic/cytotoxic drug: protein kinase inhibitor .
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 88.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to compare tumor response, progression free survival (PFS) and
      overall survival (OS) in newly diagnosed mRCC patients treated with Intuvax (INN:
      ilixadencel) pre-nephrectomy followed by Sunitinib post-nephrectomy vs Sunitinib
      post-nephrectomy patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Newly (<6 months) diagnosed RCC (histological/cytological verification is optional)
             with at least one (1) CT-verified metastasis ≥10mm 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 5-8 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 x10e9/L

               -  B-Platelet count ≥150 x10e9/L

               -  B-Hemoglobin ≥90 g/L

          8. S-creatinine and S-bilirubin ≤ 1.5 x upper limit of normal (ULN). Serum alanine
             aminotransferase (S-ALAT) and serum aspartate aminotransferase (S-ASAT) ≤ 2.5 x 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]) Female of childbearing potential must have a negative from
             Screening until 90 days after last dose of Intuvax and/or until completed sunitinib
             treatment whichever occurs later.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.

        Exclusion Criteria:

          1. Life expectancy less than 4 months

          2. Central nervous system (CNS) metastasis that is symptomatic or progressing or
             untreated or that required 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, systemic lupus erythematosus (SLE),
             vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other
             rheumatological diseases

          4. Treatment with per oral systemic corticosteroids exceeding 10mg/day within seven (7)
             days before Screening until nephrectomy (inhaled, intranasal and local steroids
             accepted irrespective of dose)

          5. Known cardiomyopathy and/or clinical significant abnormal ECG findings at Screening
             disqualifying the patient from nephrectomy and from subsequent sunitinib treatment

          6. 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 before 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, hepatitis B and hepatitis C)

         15. Eastern Cooperative Oncology Group (ECOG) performance status >2 after optimization of
             analgesics

         16. Abnormal and clinical 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 summary of product characteristics
                  (SmPC) / United States prescribing information (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 sunitinib or to chemically related products or
             likely to be exacerbated to by any component of the study products

         19. Prior systemic antitumour therapy within 28 days before Screening Visit. However,
             local radiation therapy to any area except for the abdominal/retroperitoneal area
             including the kidney tumour 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