IMA901 in Advanced Renal Cell Carcinoma Patients With Measurable Disease

Renal Cell Carcinoma Clinical Trial

— IMA901-202  

Official title:

Phase 2, Randomized, Open Label, Multicenter Study of Intradermal IMA901 Plus GM-CSF With or Without Low Dose Cyclophosphamide Pre-treatment in Advanced Renal Cell Carcinoma Patients With Measurable Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00523159
• Other study ID #: EudraCT Nr: 2006-006370-25
• Status: Completed
• Phase: Phase 2
• First received: August 30, 2007
• Last updated: July 9, 2012
• Start date: May 2007
• Est. completion date: August 2009

Study information

• Verified date: February 2010
• Source: immatics Biotechnologies GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutAustria: Agency for Health and Food SafetyBulgaria: Bulgarian Drug AgencyHungary: National Institute of PharmacyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSlovakia: State Institute for Drug ControlRomania: State Institute for Drug ControlSpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• 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
• IMA901 and Leukine
Intradermal injection of GM-CSF followed by intradermal injection of IMA901

Locations

Country	Name	City	State
Austria	Medizinische Universität Salzburg - Universitätsklinik für Innere Medizin III	Salzburg
Bulgaria	National Oncology Hospital - Urology	Sofia
Bulgaria	Regional Oncodispensary with inpatient sector-Sofia District	Sofia
Germany	Charité Campus Benjamin Franklin - Medizinische Klinik III	Berlin
Germany	Charité Campus Mitte-Klinik für Urologie	Berlin
Germany	Zeisigwaldkliniken Bethanien Chemnitz GmbH	Chemnitz
Germany	Universitätsklinikum Essen	Essen
Germany	Klinik der Johann-Wolfgang-Goethe-Universität	Frankfurt / 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	Tuebingen
Germany	Schwarzwald-Baar-Klinik - Abt. Hämatologie und Onkologie	Villingen-Schwenningen
Hungary	DRC Gyógyszervizsgáló Központ Kft	Balatonfüred
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	Semmelweis Egyetem - Urológiai Klinika	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
Poland	Klinika Chemioterapii Nowotworow - Uniwersytetu Medycznego	Lodz
Poland	Klinika Onkologii Wojskowego Institutu Medycznego	Warszawa
Poland	Clinic of Urology and Urological Oncology Medica University Hospital	Wroclaw
Romania	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
Slovakia	National Cancer Institut - "Narodny onkologicky ustav"	Bratislava
Slovakia	Clinic of Radiotherapy and Oncology - East Slovak Oncology Institute	Kosice
Slovakia	Martin Faculty Hospital	Martin
Slovakia	Department of Clinical Oncology - Faculty Hospital with Policlinic of J.A. Reiman	Presov
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Clinica Universitaria de Navarra - Servicio de Oncologia	Pamplona
Switzerland	University Hospital - Medicine Oncology	Geneva
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
immatics Biotechnologies GmbH

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease control rate		after 26 weeks	No
Secondary	Tumor response rates and SD rate		after 26 and 38 weeks	No
Secondary	Duration of response		from the time response is first documented until the first date of recurrence or PD	No
Secondary	Time to response		From Visit c to PR or CR	No
Secondary	TTP		From visit C to until tumor progression	No
Secondary	PFS and OS		From visit C to tumor progression or death	No
Secondary	DCR		after 38 weeks on study	No
Secondary	Immune response		Visit C, 1, 5, 6, 7, 10 and 14	No
Secondary	Effect of cyclophosphamide pre-treatment on immune response		Visit C, 1, 5,6,7, 10, 14	No
Secondary	Safety		From inclusion on the study until 3 weeks after end of study visit	Yes