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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)

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ClinicalTrials.gov Identifier: NCT02432846
Recruitment Status : Completed
First Posted : May 4, 2015
Last Update Posted : September 4, 2019
Sponsor:
Collaborators:
TFS Trial Form Support
Accelovance
Information provided by (Responsible Party):
Immunicum AB

Tracking Information
First Submitted Date  ICMJE April 15, 2015
First Posted Date  ICMJE May 4, 2015
Last Update Posted Date September 4, 2019
Study Start Date  ICMJE April 2015
Actual Primary Completion Date August 9, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2017)
  • Overall survival (OS) from randomization overall in mRCC patients and by each subgroup i.e. in high-risk and in intermediate risk mRCC patients. [ Time Frame: up to 5 years after end of study ]
  • 18 months survival rate from randomization overall in mRCC patients and by each subgroup i.e. in high risk and intermediate risk mRCC patients. [ Time Frame: up to 18 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
Median overall survival (OS) from randomization for high-risk patients [ Time Frame: up to 18 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2017)
  • Frequency and proportion of AEs including clinical significant changes in laboratory tests and vital signs from screening. [ Time Frame: up to 18 months ]
  • Progression free survival (PFS) from start of Sunitinib according to RECIST 1.1. [ Time Frame: up to 18 months ]
  • Proportion of objective response rate (ORR) from start of sunitinib treatment and duration of response in each subgroup. [ Time Frame: up to 18 months ]
  • Time to progression (TTP) from start of sunitinib treatment [ Time Frame: up to 18 months ]
  • Relative number of tumor infiltrating CD8+ TCells in the resected primary tumor compared to related number of infiltrating CD8+ TCells in available diagnostic pre-biopsy (sample from either primary tumor or metastasis acceptable) [ Time Frame: 2 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
  • Safety and tolerability as measured by characterization of AEs (frequency and severity) including clinical significant changes in laboratory tests, Child-Pugh score, and vital signs from Screening. [ Time Frame: up to 80 weeks ]
  • Median survival rate from randomization for intermediate risk patients [ Time Frame: up to 18 months ]
  • Progression free survival (PFS) from screening for intermediate risk patients [ Time Frame: up to 18 months ]
  • PFS according from Sunitinib Start for intermediate risk patients [ Time Frame: up to 18 months ]
  • PFS from Sunitinib Start for high-risk patients [ Time Frame: up to 18 months ]
  • Number of intermediate- and high- risk mRCC patients with Complete Response (CR), Partial Response (PR), Progressive Disease (PD), Stable Disease (SD), and "Not Evaluable" after 12 weeks from Sunitinib Start [ Time Frame: up tp 80 weeks ]
  • Number of infiltrating CD8+ T-cells in the resected primary renal tumor, adjacent normal kidney tissue, and if applicable of metastases renal tumor [ Time Frame: 2 months ]
Current Other Pre-specified Outcome Measures
 (submitted: June 14, 2019)
  • Proportion of patients with improved Eastern Cooperative Oncology Group (ECOG) performance status from screening. [ Time Frame: up to 18 months ]
  • Proportion of patients with improved QoL (EORTC QLQ-C30) from screening to nephrectomy visit and at 6, 12, 24, 36, 48 and 60 weeks and at end of study in scoring of global health status, physical-, role-, emotional-, cognitive- and social functioning. [ Time Frame: up to 18 months ]
  • examination of immunohistology parameters (CD3, CD4, CD56, CD68, CD163, PD-1, PD-1 Ligand, HLA Class I and II positive cells) in one (1) biopsy from teh resected primary tumor (tumor biopsy number 1) [ Time Frame: 2 months ]
  • Examination of immunohistology parameters (CD8+ TCells) in a biopsy from adjacent normal kidney tissue collected approximately 2 cm from the tumor margin and in a metastasis biopsy if applicable. [ Time Frame: 2 months ]
  • Evaluation of the correlation between degree of MHC mismatch (HLA-A, HLA-B and HLA-DRB1) between Intuvax (donor) and the patient (receiver) and intratumoral infiltration of CD8+ TCells. [ Time Frame: 2 months ]
  • Evaluation of auto- and alloimmunization parameters. [ Time Frame: up to 17 weeks ]
  • Time to treatment failure (TTF) defined as progressing during or after treatment with Intuvax + sunitinib or sunitinib followed by the start of subsequent second line systemic therapy [ Time Frame: up to 18 months ]
  • Tumor response rate according to RECIST 1.1 criteria between screening and the first post-nephrectomy assessment overall in mRCC patients and by each subgroup, i.e. in high-risk and intermediate-risk mRCC patients [ Time Frame: up to 18 months ]
Original Other Pre-specified Outcome Measures
 (submitted: April 28, 2015)
  • Number of patients with improved Eastern Cooperative Oncology Group (ECOG) performance status from screening [ Time Frame: 80 weeks ]
  • Number of patients with improved Quality of Life (QoL) from screening [ Time Frame: 80 weeks ]
  • Routine histology of resected primary renal tumor, adjacent normal kidney tissue, and if applicable of metastases [ Time Frame: 2 months ]
  • Analyses of immunohistological markers (CD3, CD4, CD56, CD68, CD133, PD1, PD1 ligand, Human Leucocyte Antigen (HLA) class I and II) for the resected primary renal tumor, adjacent normal kidney tissue, and if applicable of metastases [ Time Frame: 2 months ]
  • Investigate autoimmunization by analyzing anti-nuclear antibodies (IF-ANA) and kidney parenchyma-associated autoantigens before and after vaccination. [ Time Frame: up to 80 weeks ]
  • Investigate potential vaccine induced alloimmunization at the humoral level by screening of alloantibodies against HLA class I and II antigens before and after vaccination. [ Time Frame: up to 80 weeks ]
 
Descriptive Information
Brief Title  ICMJE Intratumoral Vaccination With Intuvax Pre-nephrectomy Followed by Sunitinib Post-nephrectomy vs Sunitinib Post-nephrectomy in Newly Diagnosed Metastatic Renal Cell Carcinoma (mRCC)
Official Title  ICMJE An Open-label, Randomized, Controlled, Multicenter, Phase II Study Evaluating Safety and Efficacy of Intratumorally Administered Intuvax Pre-nephrectomy Followed by Sunitinib Post-nephrectomy, Compared to Sunitinib Post-nephrectomy in Metastatic Renal Cell Carcinoma Patients
Brief 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 pre-nephrectomy followed by Sunitinib post-nephrectomy vs Sunitinib post-nephrectomy in non-vaccinated patients.
Detailed 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+ Sunitinib or Sunitinib alone.

Two doses of Intuvax 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 AB to further investigate the possibility of exploiting Intuvax vaccination when combined with Sunitinib for the treatment of mRCC patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Renal Cell Carcinoma, Metastatic
Intervention  ICMJE
  • Biological: Intuvax (ilixadencel)
    Therapeutic vaccine: allogeneic, pro-inflammatory dendritic cells.
    Other Name: COMBIG-DC
  • Drug: Sunitinib
    Cytostatic/cytotoxic drug: protein kinase inhibitor .
    Other Name: Sutent
Study Arms  ICMJE
  • Experimental: Intuvax+ Nephrectomy+Sunitinib
    Two Intuvax (ilixadencel) vaccinations (10 milj cells/vaccination) 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).
    Interventions:
    • Biological: Intuvax (ilixadencel)
    • Drug: Sunitinib
  • Active Comparator: Nephrectomy+Sunitinib
    Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
    Intervention: Drug: Sunitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 23, 2018)
88
Original Estimated Enrollment  ICMJE
 (submitted: April 28, 2015)
90
Actual Study Completion Date  ICMJE August 9, 2019
Actual Primary Completion Date August 9, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 ULN. S-ALAT and 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. CNS metastasis that is symptomatic or progressing or untretaed 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. 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 beeing treated with anticoagulants are excluded if teh 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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   France,   Hungary,   Latvia,   Poland,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02432846
Other Study ID Numbers  ICMJE IM-201
2014-004510-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Immunicum AB
Study Sponsor  ICMJE Immunicum AB
Collaborators  ICMJE
  • TFS Trial Form Support
  • Accelovance
Investigators  ICMJE
Principal Investigator: Börje Ljungberg, MD, Prof Umeå University Hospital
PRS Account Immunicum AB
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP