IMA901 in Advanced Renal Cell Carcinoma Patients With Measurable Disease

NCT ID: NCT00523159

Last Updated: 2012-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2009-08-31

Brief Summary

This study was conducted in order to evaluate the efficacy and safety of the cancer vaccine IMA901 and GM-CSF as adjuvant in the treatment of advanced renal cell carcinoma.

Patients received vaccination with GM-CSF followed by IMA901 during the study period of 9 months. Patients received pre-treatment with a single i.v. infusion of cyclophosphamide prior to the first vaccination.

Detailed Description

This is a multicenter, open label, randomized phase 2 study which investigated the effect of a second-line systemic treatment with IMA901 plus GM-CSF in RCC patients. Randomization was done according to a pre-treatment with low-dose cyclophosphamide (CY). Secondary endpoints comprised tumor response parameters.

The study population consisted of HLA-A*02-positive men or women with advanced RCC of the clear-cell type classified as having a favorable or intermediate risk after first-line systemic therapy for. Patients had to be aged 18 years or older, had at least have one measurable tumor lesion and had have received first-line tyrosine kinase inhibitor or cytokine systemic therapy for advanced disease, during or after which the patient had experienced disease progression.

Patients in both arms received a total of 17 vaccinations with GM-CSF followed by IMA901 during the 9 month treatment period.

At screening baseline tumor status was assessed by CT or MRI. During the study tumor assessments were performed every 6 weeks.

Immunomonitoring (T-cell responses to peptides contained in IMA901 and analysis of other immune cell populations that may influence T-cell responses), serum levels of antibodies and molecules with suspected influence on immune response were assessed on several occasions during the study.

Safety assessment comprised continuous adverse event reporting, regular physical examinations and regular assessments of vital signs, hematology, blood chemistry and urine. A 12-lead ECG was performed at screening and at the end of the study. Pregnancy testing was performed according to applicable legislation in the country where the trial was performed. At the very least, women of childbearing potential had have to undergo a pregnancy test during screening for the study, before the first dose was applied and at the end of the study.

Conditions

Renal Cell Carcinoma

Keywords

clear cell renal cell carcinoma

Study Design

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

Study Groups

1

Pre-treatment with a single low dose of Cyclophosphamide followed by IMA901 vaccination plus GM-CSF as adjuvant

Group Type: OTHER

Endoxana, IMA901, Leukine

Intervention Type: DRUG

a single i.v. infusion of Cyclophosphamid and then patients received vaccination therapy with intradermal (i.d.) injections of GM-CSF followed by i.d. injections of IMA901

2

No pre-treatment with Cyclophosphamide before vaccination with IMA901 and GM-CSF as adjuvant

Group Type: OTHER

IMA901 and Leukine

Intervention Type: DRUG

Intradermal injection of GM-CSF followed by intradermal injection of IMA901

Interventions

Endoxana, IMA901, Leukine

a single i.v. infusion of Cyclophosphamid and then patients received vaccination therapy with intradermal (i.d.) injections of GM-CSF followed by i.d. injections of IMA901

Intervention Type: DRUG

IMA901 and Leukine

Intradermal injection of GM-CSF followed by intradermal injection of IMA901

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged at least 18 years
• HLA type: HLA-A*02-positive
• Histologically documented advanced clear-cell RCC
• Patients who have received first-line tyrosine kinase inhibitor or cytokine systemic therapy for advanced disease systematic therapy for advanced disease and must be candidates for second-line therapy (NOTE: in Germany and Austria only patients after first-line tyrosine kinase inhibitor failure will be included into the study)
• Patients having experienced documented tumor progression
• At least one unidimensional measurable target lesion
• Karnofsky Performance Status ≥ 80%
• Favorable or intermediate risk according to the 3-score MSKCC criteria.
• Able to understand the nature of the study and give written informed consent
• Willingness and ability to comply with the study protocol for the duration of the study

Exclusion Criteria

• Poor risk according to the 3-score MSKCC criteria
• Immunosuppressive therapy within 4 weeks before study entry, e.g. corticosteroid treatment
• History of other malignant tumors, except non-melanoma-skin cancer or curatively excised cervical carcinoma in situ
• Presence of brain metastases on MRI or CT scan
• Patients with a history or evidence of systemic autoimmune disease
• Any vaccination in the two weeks before study entry
• Any planned prophylactic vaccination from study entry until the end of the induction period (5 weeks after the first vaccination)
• Known active hepatitis B or C infection
• Known HIV infection
• Any other infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patient tissues.
• Any of the following in the 4 weeks before study entry:

1. Major surgery

2. Anticancer treatments including (but not limited to) cytotoxic chemotherapy, radiotherapy, immunotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies

3. Unresolved toxicity from prior anticancer treatments including (but not limited to) cytotoxic chemotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies, radiotherapy, or immunotherapy

4. Received study drug within any clinical study

• Any of the following abnormal laboratory values:

1. Hematology: Hb < 9 g/dL; WBC < 3 x 109/L; neutrophils < 1.5 x 109/L; lymphocytes < 1.0 x 109/L; platelets < 100 x 109/L

2. Liver function: serum bilirubin > 1.5 x upper normal limit (unless a history of Gilbert's disease); ALAT or ASAT > 3 x upper normal limit (>5 x upper normal limit if liver metastases are present)

3. Renal function: serum creatinine > 200 µmol/L

• Patients with other significant diseases currently uncontrolled by treatment which might interfere with study completion, for example:

1. Heart failure or non compensated active heart disease

2. Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension

3. Symptomatic neurotoxicity (motor or sensory) ≥ grade 2 National Cancer Institute - Common Toxicity Criteria (NCI-CTC).

4. Severe pulmonary dysfunction

• Psychiatric disabilities, seizures or central nervous system disorders that may interfere with the ability to give informed consent or perform adequate follow-up in the investigator's opinion
• Active infections requiring oral or intravenous antibiotics
• Women or men who decline to practice a medically approved method of contraception
• Pregnancy or breastfeeding
• Any condition which in the judgment of the investigator would place the patient at undue risk or interfere with the results of the study

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

Sponsors

Immatics Biotechnologies GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandra Kirner, PhD

Role: STUDY_DIRECTOR

Immatics Biotechnologies GmbH

Locations

Medizinische Universität Salzburg - Universitätsklinik für Innere Medizin III

Salzburg, , Austria

National Oncology Hospital - Urology

Sofia, , Bulgaria

Regional Oncodispensary with inpatient sector-Sofia District

Sofia, , Bulgaria

Charité Campus Mitte-Klinik für Urologie

Berlin, , Germany

Charité Campus Benjamin Franklin - Medizinische Klinik III

Berlin, , Germany

Zeisigwaldkliniken Bethanien Chemnitz GmbH

Chemnitz, , Germany

Universitätsklinikum Essen

Essen, , Germany

Klinik der Johann-Wolfgang-Goethe-Universität

Frankfurt am Main, , Germany

Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum (Onkologie / Hämatologie)

Hamburg, , Germany

Universitätsklinikum Heidelberg - Klinik für Urologie

Heidelberg, , Germany

Universitätsklinikum Schleswig Holstein - Campus Lübeck

Lübeck, , Germany

Universitätsklinikum Mainz - 3. Medizinische Klinik

Mainz, , Germany

Klinikum der Universität - München Großhadern

Munich, , Germany

Urologische Klinik Dr. Castringius - München-Planegg

Planegg, , Germany

Universitätsklinikum Tübingen - Klinik für Urologie

Tübingen, , Germany

Schwarzwald-Baar-Klinik - Abt. Hämatologie und Onkologie

Villingen-Schwenningen, , Germany

DRC Gyógyszervizsgáló Központ Kft

Balatonfüred, , Hungary

Semmelweis Egyetem - Urológiai Klinika

Budapest, , Hungary

Bajcsy-Zsilinszky Kórház - Urológia Osztály

Budapest, , Hungary

Fövárosi Önk.Szt.Imre Kórház - Belgyógyászat-Kliniko-FFarmakológia

Budapest, , Hungary

Országos Onkológiai Intézet - Kemoterápia C osztály-Klinikofarmakológia

Budapest, , Hungary

Debreceni Egyetem Orvos és Egészségtudományi Centrum

Debrecen, , Hungary

Hajdú-Bihar Megyei Önk. Kenézy Gyula Kórház/Urológia Osztály

Debrecen, , Hungary

BAZ megyei Kórház - Urológia Osztály

Miskolc, , Hungary

Pécs Orvostudomanyi Egyetem - Urológiai Klinika

Pécs, , Hungary

Klinika Chemioterapii Nowotworow - Uniwersytetu Medycznego

Lodz, , Poland

Klinika Onkologii Wojskowego Institutu Medycznego

Warsaw, , Poland

Clinic of Urology and Urological Oncology Medica University Hospital

Wroclaw, , Poland

Oncology Institute "Prof. Dr. Alexandru Trestioreanu"

Bucharest, , Romania

Oncology Institute - "Prof. Dr. Alexandru Trestioreanu"

Bucharest, , Romania

Oncology Institute "Prof. Dr. Ion Chiricuta"

Cluj-Napoca, , Romania

Clinical County Hospital Oradea

Oradea, , Romania

National Cancer Institut - "Narodny onkologicky ustav"

Bratislava, , Slovakia

Clinic of Radiotherapy and Oncology - East Slovak Oncology Institute

Košice, , Slovakia

Martin Faculty Hospital

Martin, , Slovakia

Department of Clinical Oncology - Faculty Hospital with Policlinic of J.A. Reiman

Prešov, , Slovakia

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Puerta de Hierro

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Clinica Universitaria de Navarra - Servicio de Oncologia

Pamplona, , Spain

University Hospital - Medicine Oncology

Geneva, , Switzerland

Beatson Oncology Centre

Glasgow, , United Kingdom

Christie Hospital NHS Trust, CRUK Department of Medical Onkology - Paterson Institute for Cancer Research

Manchester, , United Kingdom

University of Surrey - Postgraduate Medical School

Surrey, , United Kingdom

Countries

Austria; Bulgaria; Germany; Hungary; Poland; Romania; Slovakia; Spain; Switzerland; United Kingdom

Other Identifiers

EudraCT Nr: 2006-006370-25

Identifier Type: -

Identifier Source: org_study_id