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
Overview
- Phase
- Phase 2
- Intervention
- Sunitinib
- Conditions
- Renal Cell Carcinoma, Metastatic
- Sponsor
- Mendus
- Enrollment
- 88
- Locations
- 28
- Primary Endpoint
- 18-Months' Overall Survival Percentage (PPS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •Planned resection of primary tumor
- •Primary tumor diameter ≥40 mm
- •Candidate for first-line therapy with sunitinib initiated 5-8 weeks after nephrectomy
- •Female or male ≥18 years of age
- •Willing and able to provide informed consent
- •Adequate hematological parameters, i.e:
- •B-Leukocyte count ≥4.5 x10e9/L
- •B-Platelet count ≥150 x10e9/L
- •B-Hemoglobin ≥90 g/L
Exclusion Criteria
- •Life expectancy less than 4 months
- •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)
- •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
- •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)
- •Known cardiomyopathy and/or clinical significant abnormal ECG findings at Screening disqualifying the patient from nephrectomy and from subsequent sunitinib treatment
- •Karnofsky performance status \<70%
- •National Cancer Institute (NCI) Common Terminology criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within 28 days before Screening
- •Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
- •Clinically significant gastrointestinal abnormalities
- •Uncontrolled hypertension, or uncontrolled diabetes mellitus
Arms & Interventions
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).
Intervention: Sunitinib
Nephrectomy+Sunitinib
Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Intervention: Sunitinib
Outcomes
Primary Outcomes
18-Months' Overall Survival Percentage (PPS)
Time Frame: At 18 months (544 days)
The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization.
18-Months' Overall Survival Percentage (FAS)
Time Frame: At 18 months (544 days)
The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization.
Overall Survival (OS) - Days (FAS)
Time Frame: From the randomization to the date of death, up to 5 years after the last participant's 18-month survival data.
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.
Overall Survival - Days (PPS)
Time Frame: From the randomization to the date of death, up to 5 years after the last patient's 18-month survival data.
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.
Secondary Outcomes
- Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1.(From Sunitinib-Start to progressive disease or death, up to 18 months.)
- Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup.(From start of sunitinib treatment up to 18 months)
- Number of Participants With Specific Best Overall Response(From start of sunitinib treatment up to 18 months)
- Disease Control Rate(From start of sunitinib treatment up to 18 months)
- Duration of Response(From first date of CR or PR until date of PD or death, up to 18 months.)
- Duration of Clinical Benefit(From first date of clinical benefit (CR, PR or SD) until date of PD or death, up to 18 months.)
- Duration of Stable Disease(From first date of SD until PD or date of death, up to 18 months.)
- Time to Progression (TTP)(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.)
- Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells(At resection of primary tumor.)