Clinical trial NCT02432846: 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: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cell Carcinoma, Metastatic
Lead sponsor: Mendus
Sponsor class: INDUSTRY
Collaborators: name: TFS Trial Form Support
name: Accelovance
First posted: 2015-05-04
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 (INN: ilixadencel) pre-nephrectomy followed by Sunitinib post-nephrectomy vs Sunitinib post-nephrectomy 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 (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.

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

Primary outcomes:
measure: Overall Survival (OS) - Days (FAS)
timeFrame: From the randomization to the date of death, up to 5 years after the last participant's 18-month survival data.
measure: Overall Survival - Days (PPS)
timeFrame: From the randomization to the date of death, up to 5 years after the last patient's 18-month survival data.
measure: 18-Months' Overall Survival Percentage (FAS)
timeFrame: At 18 months (544 days)
measure: 18-Months' Overall Survival Percentage (PPS)
timeFrame: At 18 months (544 days)
Secondary outcomes:
measure: Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1.
timeFrame: From Sunitinib-Start to progressive disease or death, up to 18 months.
measure: Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup.
timeFrame: From start of sunitinib treatment up to 18 months
measure: Number of Participants With Specific Best Overall Response
timeFrame: From start of sunitinib treatment up to 18 months
measure: Disease Control Rate
timeFrame: From start of sunitinib treatment up to 18 months
measure: Duration of Response
timeFrame: From first date of CR or PR until date of PD or death, up to 18 months.
measure: Duration of Clinical Benefit
timeFrame: From first date of clinical benefit (CR, PR or SD) until date of PD or death, up to 18 months.
measure: Duration of Stable Disease
timeFrame: From first date of SD until PD or date of death, up to 18 months.
measure: Time to Progression (TTP)
timeFrame: Time from Sunitinib-Start to date of either PD according to RECIST 1.1 or clinical progression as evaluated by the Investigator, up to 18 months.
measure: Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells
timeFrame: At resection of primary tumor.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Saint Paul
country: United States
facility: Health Partners Institute
state: Minnesota
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Angers Cedex 9
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse-Hôpital Rangueil
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Szeged
country: Hungary
facility: Szent-Györgyi Albert Klinikai Központ
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital
city: Kraków
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej Vesalius Sp. z o.o.
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
city: Warsaw
country: Poland
facility: Military Institute of Medicine
city: Wieliszew
country: Poland
facility: Mazowiecki Szpital Onkologiczny
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Sabadell
country: Spain
facility: Hospital Universitari Parc Tauli
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Huddinge
country: Sweden
facility: Karolinska University Hospital
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Oxford
country: United Kingdom
facility: The Churchill Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
Study officials:
affiliation: Umeå University Hospital
name: Börje Ljungberg, MD, Prof
role: PRINCIPAL_INVESTIGATOR
References: