Phase 2, randomised, 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

• Conditions: HLA-A*02-positive patients with advanced clear cell RCC who have progressed during or after previous systemic therapy for advanced disease and have a favourable or intermediate risk after systemic therapy according to the 3-score risk cc prognostic risk category (Motzer 2004).

• Registration Number: EUCTR2006-006370-25-AT
• Lead Sponsor: immatics biotechnologies GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-05-24
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

1.Aged at least 18 years
2.HLA type: HLA-A*02-positive
3.Histologically documented advanced clear-cell RCC
4.Patients who have received first-line tyrosine kinase inhibitor systemic therapy for advanced disease and are candidates for second-line therapy. Patients who have received treatment with two sequential tyrosine kinase inhibitors are also accepted.
5.Patients having experienced documented tumor progression during or after previous systemic therapy. Documentation of progression must be either imaging based (i.e. any increase in lesion size and/or an increase in the number of tumor lesions) or based on clinical (symptomatic) tumor progression.
6.At least one unidimensional measurable target lesion documented by adequate imaging and assessable according to the RECIST criteria, whereby target lesions must not lie in a previously irradiated area
7.Karnofsky Performance Status lower than 80
8.Favorable or intermediate risk according to the 3-score MSKCC criteria (see Section 4.5.3 of the protocol). The subject has a favorable risk if none, or intermediate risk if only one of the following criteria applies (if two or three criteria apply the subject is not eligible):
a. Karnofsky performance status lower than 80
b. Serum haemoglobin = 13 g/dL for males and = 11.5 g/dL for females
c. Corrected serum calcium = 10 mg/dL
9.Able to understand the nature of the study and give written informed consent
10.Willingness and ability to comply with the study protocol for the duration of the study

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1)Poor risk according to the 3-score MSKCC criteria (see Section 4.5.3 of the protocol).
2)Immunosuppressive therapy within 4 weeks before Visit C, e.g. corticosteroid treatment (exceptions are corticosteroid substitution therapy for adrenal insufficiency or inhalative corticosteroids for e.g. asthma)
3)History of other malignant tumors, except basal cell carcinoma or curatively excised cervical carcinoma in situ
4)Presence of brain metastases on MRI or CT scan
5)Patients with a history or evidence of systemic autoimmune disease
6)Any vaccination in the two weeks before Visit C
7)Any planned prophylactic vaccination from study entry until the end of the induction period (5 weeks after the first vaccination)
8)Known active hepatitis B or C infection
9)Known HIV infection
10)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. Examples are: rabies, mycobacterium tuberculosis, coccidiodes immitis.
11)Any of the following in the 4 weeks before Visit C:
a)Major surgery
b)Anticancer treatments including (but not limited to) cytotoxic chemotherapy, radiotherapy, immunotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies
c)Unresolved toxicity from prior anticancer treatments including (but not limited to) cytotoxic chemotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies, radiotherapy, or immunotherapy
d)Received study drug within any clinical study (including approved and experimental drugs)
12)Any of the following abnormal laboratory values:
a)Hematology: Hb < 9 g/dL; WBC < 3 x 10^9/L; neutrophils < 1.5 x 10^9/L; lymphocytes < 1.0 x 10^9/L; platelets < 100 x 10^9/L
b)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)
c)Renal function: serum creatinine > 200 µmol/L
13)Patients with other significant diseases currently uncontrolled by treatment which might interfere with study completion, including gastrointestinal, hepatic, renal, respiratory, cardiovascular, hematological, coagulation, metabolic or hormonal diseases with clinically relevant abnormal organ function for example:
a)Heart failure or non compensated active heart disease (= New York Heart Association III, see Appendix 2 of the protocol)
b)Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension
c)Symptomatic neurotoxicity (motor or sensory) = grade 2 National Cancer Institute – Common Toxicity Criteria (NCI-CTC).d)Severe pulmonary dysfunction
14)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
15) Active infections requiring oral or intravenous antibiotics
16)Women or men who decline to practice a medically approved method of contraception
17)Pregnancy or breastfeeding
18)Any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study (e.g. poor medical risks because of non malignant disease, or secondary effects of cancer)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the present phase 2 study is to determine whether IMA901 as single agent with GM-CSF as adjuvant shows sufficient anti-tumor efficacy in patients with advanced RCC to warrant further development.;Secondary Objective: Secondary objectives of this study are safety, immunological parameters, the potential of low-dose cyclophosphamide (CY) to improve immune response to IMA901, and additional efficacy endpoints.;Primary end point(s): The primary endpoint of this study is defined as the DCR at Visit 14 (after 26 weeks of treatment). This endpoint represents a composite of the objective response rate (ORR) and stable disease (SD) rate, where ORR is defined as the complete response (CR) rate plus partial response (PR) rate. All deaths regardless of cause will be considered as events for the assessment of DCR. The assessment of the primary endpoint will be based on RECIST as described in section 8.1.7 and the imaging charter for central review.