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

NCT ID: NCT02432846

Last Updated: 2022-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2021-01-31

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.

Conditions

Renal Cell Carcinoma, Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intuvax (INN: ilixadencel)+ Nephrectomy+Sunitinib

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).

Group Type: EXPERIMENTAL

Intuvax (INN: ilixadencel)

Intervention Type: BIOLOGICAL

Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.

Sunitinib

Intervention Type: DRUG

Cytostatic/cytotoxic drug: protein kinase inhibitor .

Nephrectomy+Sunitinib

Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).

Group Type: ACTIVE_COMPARATOR

Sunitinib

Intervention Type: DRUG

Cytostatic/cytotoxic drug: protein kinase inhibitor .

Interventions

Intuvax (INN: ilixadencel)

Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.

Intervention Type: BIOLOGICAL

Sunitinib

Cytostatic/cytotoxic drug: protein kinase inhibitor .

Intervention Type: DRUG

Other Intervention Names

COMBIG-DC; Sutent

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TFS Trial Form Support

INDUSTRY

Sponsor Role: collaborator

Accelovance

INDUSTRY

Sponsor Role: collaborator

Mendus

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Börje Ljungberg, MD, Prof

Role: PRINCIPAL_INVESTIGATOR

Umeå University Hospital

Locations

University of Illinois

Chicago, Illinois, United States

Rush University

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

Health Partners Institute

Saint Paul, Minnesota, United States

Duke Cancer Institute

Durham, North Carolina, United States

University Hospital Olomouc

Olomouc, , Czechia

Centre Hospitalier Universitaire d'Angers

Angers, , France

Centre Hospitalier Universitaire de Toulouse-Hôpital Rangueil

Toulouse, , France

University of Debrecen

Debrecen, , Hungary

Szent-Györgyi Albert Klinikai Központ

Szeged, , Hungary

Pauls Stradins Clinical University Hospital

Riga, , Latvia

Riga East Clinical University Hospital

Riga, , Latvia

Niepubliczny Zakład Opieki Zdrowotnej Vesalius Sp. z o.o.

Krakow, , Poland

Wojewodzki Szpital Specjalistyczny

Lublin, , Poland

Military Institute of Medicine

Warsaw, , Poland

Mazowiecki Szpital Onkologiczny

Wieliszew, , Poland

Hospital Universitari Germans Trias i Pujol

Badalona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, , Spain

Hospital Universitari Parc Tauli

Sabadell, , Spain

Sahlgrenska University Hospital

Gothenburg, , Sweden

Karolinska University Hospital

Huddinge, , Sweden

Umeå University Hospital

Umeå, , Sweden

Uppsala University Hospital

Uppsala, , Sweden

The Churchill Hospital

Oxford, , United Kingdom

Royal Preston Hospital

Preston, , United Kingdom

Countries

United States; Czechia; France; Hungary; Latvia; Poland; Spain; Sweden; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-004510-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IM-201

Identifier Type: -

Identifier Source: org_study_id