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Intratumoral Vaccination With Intuvax Pre-nephrectomy Followed by Sunitinib Post-nephrectomy vs Sunitinib Post-nephrectomy in Newly Diagnosed Metastatic Renal Cell Carcinoma (mRCC) (MERECA)

M

Mendus

Status and phase

Completed
Phase 2

Conditions

Renal Cell Carcinoma, Metastatic

Treatments

Biological: Intuvax (INN: ilixadencel)
Drug: Sunitinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT02432846
IM-201
2014-004510-28 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

Patients, all planned for nephrectomy, will be stratified according to the Heng risk criteria (high risk patients vs. intermediate risk patients) and randomized in a 2:1 ratio to receive Intuvax (INN: ilixadencel)+ Sunitinib or Sunitinib alone.

Two doses of Intuvax (INN: ilixadencel) will be administered in to the primary tumour before nephrectomy. The control group will be scheduled for nephrectomy directly.

All patients will start Sunitinib treatment 5-8 weeks after operation.

Results from the phase I study, together with the results reported in the literature on the use of autologous dendritic cells (DCs) in combination with Sunitinib encourage Immunicum aktiebolag (AB) to further investigate the possibility of exploiting Intuvax (INN: ilixadencel) 10 million cells/dose when combined with Sunitinib for the treatment of mRCC patients.

Enrollment

88 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

88 participants in 2 patient groups

Intuvax (INN: ilixadencel)+ Nephrectomy+Sunitinib
Experimental group
Description:
Two Intuvax (INN: ilixadencel) doses (10 million cells/dose) 14 days apart before nephrectomy, followed by Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Treatment:
Drug: Sunitinib
Biological: Intuvax (INN: ilixadencel)
Nephrectomy+Sunitinib
Active Comparator group
Description:
Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Treatment:
Drug: Sunitinib

Trial documents
2

Trial contacts and locations

28

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Data sourced from clinicaltrials.gov

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