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

Renal Cell Carcinoma, Metastatic Clinical Trial

— MERECA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02432846
• Other study ID #: IM-201
• Secondary ID: 2014-004510-28
• Status: Completed
• Phase: Phase 2
• Start date: April 2015
• Est. completion date: January 31, 2021

Study information

• Verified date: July 2022
• Source: Immunicum AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: January 31, 2021
• Est. primary completion date: January 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma, Metastatic

Intervention

Biological:
• Intuvax (INN: ilixadencel)
Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.

Drug:
• Sunitinib
Cytostatic/cytotoxic drug: protein kinase inhibitor .

Locations

Country	Name	City	State
Czechia	University Hospital Olomouc	Olomouc
France	Centre Hospitalier Universitaire d'Angers	Angers Cedex 9
France	Centre Hospitalier Universitaire de Toulouse-Hôpital Rangueil	Toulouse
Hungary	University of Debrecen	Debrecen
Hungary	Szent-Györgyi Albert Klinikai Központ	Szeged
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Riga East Clinical University Hospital	Riga
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Vesalius Sp. z o.o.	Kraków
Poland	Wojewodzki Szpital Specjalistyczny	Lublin
Poland	Military Institute of Medicine	Warsaw
Poland	Mazowiecki Szpital Onkologiczny	Wieliszew
Spain	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
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Karolinska University Hospital	Huddinge
Sweden	Umeå University Hospital	Umeå
Sweden	Uppsala University Hospital	Uppsala
United Kingdom	The Churchill Hospital	Oxford
United Kingdom	Royal Preston Hospital	Preston
United States	Rush University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Duke Cancer Institute	Durham	North Carolina
United States	University of Iowa	Iowa City	Iowa
United States	Health Partners Institute	Saint Paul	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Immunicum AB	Accelovance, TFS Trial Form Support

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) - Days (FAS)	OS is the time from randomization until date of death. The patients who were alive at the end of study were followed for survival status (alive/date of death) through medical records, databases and public records according to the time frame below.; Due to censored data, estimates of upper 95% CI could not be determined in all reporting groups.	From the randomization to the date of death, up to 5 years after the last participant's 18-month survival data.
Primary	Overall Survival - Days (PPS)	OS is the time from randomization until date of death. The patients who were alive at the end of study were followed for survival status (alive/date of death) through medical records, databases and public records according to the time frame below.; Due to censored data, upper 95% CI could not be determined in all reporting groups.	From the randomization to the date of death, up to 5 years after the last patient's 18-month survival data.
Primary	18-Months' Overall Survival Percentage (FAS)	The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization.	At 18 months (544 days)
Primary	18-Months' Overall Survival Percentage (PPS)	The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization.	At 18 months (544 days)
Secondary	Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1.	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by radiographic assessment: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.; Due to the large amount of censored data, estimates of median and/or a 95% CI could not be reliably determined in all reporting groups.; Baseline data are reported for the safety data set (all patients randomized) whereas PFS is analyzed for the full analysis set (FAS). Two patients in the safety data set were not included in the FAS since they withdrew prior to start of treatment.	From Sunitinib-Start to progressive disease or death, up to 18 months.
Secondary	Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup.	Objective response rate was defined as the percentage of patients with complete response (CR) and partial response (PR).Tumor response was evaluated centrally according to the RECIST 1.1 guideline.	From start of sunitinib treatment up to 18 months
Secondary	Number of Participants With Specific Best Overall Response	The best overall response is the best response recorded from the start of the treatment sunitinib until disease progression/recurrence; taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started. In general, the patient's best response assignment depended on the achievement of the measurement criteria.	From start of sunitinib treatment up to 18 months
Secondary	Disease Control Rate	Best overall response (CR, PR or SD) evaluated from Sunitinib-Start for patients with available data.	From start of sunitinib treatment up to 18 months
Secondary	Duration of Response	The duration of response was calculated for only those patients who responded. It was the time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever came first).	From first date of CR or PR until date of PD or death, up to 18 months.
Secondary	Duration of Clinical Benefit	Disease control rate (DCR) also called Clinical Benefit Rate, was defined as the proportion of patients with CR or PR or SD.	From first date of clinical benefit (CR, PR or SD) until date of PD or death, up to 18 months.
Secondary	Duration of Stable Disease	The duration of SD was calculated for only those patients who exhibited a best response of SD response as per RECIST v1.1. It was the time from first SD response to first observed progression of disease or death if the death was due to disease progression (whichever came first), up to 18 months.	From first date of SD until PD or date of death, up to 18 months.
Secondary	Time to Progression (TTP)	Due to the large amount of censored data, estimate of upper 95% CI could not be reliably determined in all reporting groups.	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.
Secondary	Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells	Relative number of tumor-infiltrating CD8+ T-cells in the resected primary tumor compared to number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy (sample from either primary tumor or metastasis), was not to be evaluated as described in the protocol due to missing pre-biopsy samples). Instead an automated and validated quantification of percentage of CD8+ tissue in delineated tumor area was made.	At resection of primary tumor.