Clinical trial NCT00523159: IMA901 in Advanced Renal Cell Carcinoma Patients With Measurable Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: clear cell renal cell carcinoma
Lead sponsor: Immatics Biotechnologies GmbH
Sponsor class: INDUSTRY
First posted: 2007-08-31
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease control rate
timeFrame: after 26 weeks
Secondary outcomes:
measure: Tumor response rates and SD rate
timeFrame: after 26 and 38 weeks
measure: Duration of response
timeFrame: from the time response is first documented until the first date of recurrence or PD
measure: Time to response
timeFrame: From Visit c to PR or CR
measure: TTP
timeFrame: From visit C to until tumor progression
measure: PFS and OS
timeFrame: From visit C to tumor progression or death
measure: DCR
timeFrame: after 38 weeks on study
measure: Immune response
timeFrame: Visit C, 1, 5, 6, 7, 10 and 14
measure: Effect of cyclophosphamide pre-treatment on immune response
timeFrame: Visit C, 1, 5,6,7, 10, 14
measure: Safety
timeFrame: From inclusion on the study until 3 weeks after end of study visit
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: Medizinische Universität Salzburg - Universitätsklinik für Innere Medizin III
city: Sofia
country: Bulgaria
facility: National Oncology Hospital - Urology
city: Sofia
country: Bulgaria
facility: Regional Oncodispensary with inpatient sector-Sofia District
city: Berlin
country: Germany
facility: Charité Campus Mitte-Klinik für Urologie
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin - Medizinische Klinik III
city: Chemnitz
country: Germany
facility: Zeisigwaldkliniken Bethanien Chemnitz GmbH
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt / Main
country: Germany
facility: Klinik der Johann-Wolfgang-Goethe-Universität
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum (Onkologie / Hämatologie)
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg - Klinik für Urologie
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig Holstein - Campus Lübeck
city: Mainz
country: Germany
facility: Universitätsklinikum Mainz - 3. Medizinische Klinik
city: Munich
country: Germany
facility: Klinikum der Universität - München Großhadern
city: Planegg
country: Germany
facility: Urologische Klinik Dr. Castringius - München-Planegg
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tübingen - Klinik für Urologie
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar-Klinik - Abt. Hämatologie und Onkologie
city: Balatonfüred
country: Hungary
facility: DRC Gyógyszervizsgáló Központ Kft
city: Budapest
country: Hungary
facility: Semmelweis Egyetem - Urológiai Klinika
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Kórház - Urológia Osztály
city: Budapest
country: Hungary
facility: Fövárosi Önk.Szt.Imre Kórház - Belgyógyászat-Kliniko-FFarmakológia
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet - Kemoterápia C osztály-Klinikofarmakológia
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos és Egészségtudományi Centrum
city: Debrecen
country: Hungary
facility: Hajdú-Bihar Megyei Önk. Kenézy Gyula Kórház/Urológia Osztály
city: Miskolc
country: Hungary
facility: BAZ megyei Kórház - Urológia Osztály
city: Pécs
country: Hungary
facility: Pécs Orvostudomanyi Egyetem - Urológiai Klinika
city: Lodz
country: Poland
facility: Klinika Chemioterapii Nowotworow - Uniwersytetu Medycznego
city: Warszawa
country: Poland
facility: Klinika Onkologii Wojskowego Institutu Medycznego
city: Wroclaw
country: Poland
facility: Clinic of Urology and Urological Oncology Medica University Hospital
city: Bucharest
country: Romania
facility: Oncology Institute "Prof. Dr. Alexandru Trestioreanu"
city: Bucharest
country: Romania
facility: Oncology Institute - "Prof. Dr. Alexandru Trestioreanu"
city: Cluj-Napoca
country: Romania
facility: Oncology Institute "Prof. Dr. Ion Chiricuta"
city: Oradea
country: Romania
facility: Clinical County Hospital Oradea
city: Bratislava
country: Slovakia
facility: National Cancer Institut - "Narodny onkologicky ustav"
city: Kosice
country: Slovakia
facility: Clinic of Radiotherapy and Oncology - East Slovak Oncology Institute
city: Martin
country: Slovakia
facility: Martin Faculty Hospital
city: Presov
country: Slovakia
facility: Department of Clinical Oncology - Faculty Hospital with Policlinic of J.A. Reiman
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra - Servicio de Oncologia
city: Geneva
country: Switzerland
facility: University Hospital - Medicine Oncology
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust, CRUK Department of Medical Onkology - Paterson Institute for Cancer Research
city: Surrey
country: United Kingdom
facility: University of Surrey - Postgraduate Medical School
Study officials:
affiliation: Immatics Biotechnologies GmbH
name: Alexandra Kirner, PhD
role: STUDY_DIRECTOR
References: