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

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma, Metastatic	Biological: Intuvax (ilixadencel); Drug: Sunitinib	Phase 2

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 Design

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	88 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	April 2015
Estimated Primary Completion Date :	August 2019
Estimated Study Completion Date :	August 2019

Arms and Interventions

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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).	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
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).	Drug: Sunitinib; Cytostatic/cytotoxic drug: protein kinase inhibitor .; Other Name: Sutent

Outcome Measures

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. 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 ]
2. 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 ]

Secondary Outcome Measures :

1. Frequency and proportion of AEs including clinical significant changes in laboratory tests and vital signs from screening. [ Time Frame: up to 18 months ]
2. Progression free survival (PFS) from start of Sunitinib according to RECIST 1.1. [ Time Frame: up to 18 months ]
3. Proportion of objective response rate (ORR) from start of sunitinib treatment and duration of response in each subgroup. [ Time Frame: up to 18 months ]
4. Time to progression (TTP) from start of sunitinib treatment [ Time Frame: up to 18 months ]
5. 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 ]

Other Outcome Measures:

1. Proportion of patients with improved Eastern Cooperative Oncology Group (ECOG) performance status from screening. [ Time Frame: up to 18 months ]
2. 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 ]
3. 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 ]
4. 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 ]
5. 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 ]
6. Evaluation of auto- and alloimmunization parameters. [ Time Frame: up to 17 weeks ]
7. 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 ]

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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 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

Contacts and Locations

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 28 Study Locations

Sponsors and Collaborators

Immunicum AB

TFS Trial Form Support

Accelovance

Investigators

Principal Investigator:	Börje Ljungberg, MD, Prof	Umeå University Hospital

More Information

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Immunicum AB
ClinicalTrials.gov Identifier:	NCT02432846 History of Changes
Other Study ID Numbers:	IM-201; 2014-004510-28 ( EudraCT Number )
First Posted:	May 4, 2015
Last Update Posted:	February 27, 2018
Last Verified:	February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site	Kidney Diseases; Urologic Diseases; Sunitinib; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors