IMA901 in Advanced Renal Cell Carcinoma Patients With Measurable Disease (IMA901-202)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
immatics Biotechnologies GmbH
ClinicalTrials.gov Identifier:
NCT00523159
First received: August 30, 2007
Last updated: July 9, 2012
Last verified: February 2010
  Purpose

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.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: Endoxana, IMA901, Leukine
Drug: IMA901 and Leukine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by immatics Biotechnologies GmbH:

Primary Outcome Measures:
  • Disease control rate [ Time Frame: after 26 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response rates and SD rate [ Time Frame: after 26 and 38 weeks ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: from the time response is first documented until the first date of recurrence or PD ] [ Designated as safety issue: No ]
  • Time to response [ Time Frame: From Visit c to PR or CR ] [ Designated as safety issue: No ]
  • TTP [ Time Frame: From visit C to until tumor progression ] [ Designated as safety issue: No ]
  • PFS and OS [ Time Frame: From visit C to tumor progression or death ] [ Designated as safety issue: No ]
  • DCR [ Time Frame: after 38 weeks on study ] [ Designated as safety issue: No ]
  • Immune response [ Time Frame: Visit C, 1, 5, 6, 7, 10 and 14 ] [ Designated as safety issue: No ]
  • Effect of cyclophosphamide pre-treatment on immune response [ Time Frame: Visit C, 1, 5,6,7, 10, 14 ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: From inclusion on the study until 3 weeks after end of study visit ] [ Designated as safety issue: Yes ]

Enrollment: 68
Study Start Date: May 2007
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
Pre-treatment with a single low dose of Cyclophosphamide followed by IMA901 vaccination plus GM-CSF as adjuvant
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
2
No pre-treatment with Cyclophosphamide before vaccination with IMA901 and GM-CSF as adjuvant
Drug: IMA901 and Leukine
Intradermal injection of GM-CSF followed by intradermal injection of IMA901

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00523159

  Show 44 Study Locations
Sponsors and Collaborators
immatics Biotechnologies GmbH
Investigators
Study Director: Alexandra Kirner, PhD immatics Biotechnologies GmbH
  More Information

No publications provided

Responsible Party: immatics Biotechnologies GmbH
ClinicalTrials.gov Identifier: NCT00523159     History of Changes
Other Study ID Numbers: EudraCT Nr: 2006-006370-25
Study First Received: August 30, 2007
Last Updated: July 9, 2012
Health Authority: Germany: Paul-Ehrlich-Institut
Austria: Agency for Health and Food Safety
Bulgaria: Bulgarian Drug Agency
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Slovakia: State Institute for Drug Control
Romania: State Institute for Drug Control
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Switzerland: Swissmedic

Keywords provided by immatics Biotechnologies GmbH:
clear cell renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014