Clinical trial NCT01012102: EMD 640 744 in Montanide ISA 51 VG Administered in Subjects With Advanced Solid Tumors
Official title: An Open Label, Parallel Group, Randomized Phase I Study of Biological Activity, Safety, Tolerability, and Clinical Activity of Different Dose Levels of EMD 640 744 in Montanide ISA 51 VG Administered in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: EMD 640744
Montanide
Advanced solid tumours
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2009-11-11
Enrollment: 104
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: To compare 3 doses of EMD 640744 administered by subcutaneous injection in combination with Montanide® ISA 51 VG with regard to immunological efficacy.

The primary target variable is the immune response as assessed by ELISPOT before and until week 17 after vaccination with EMD 640744 in Montanide® ISA 51 VG.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects ≥18 years of age
* Signed written informed consent
* Histologically or cytologically documented metastatic or locally advanced survivin-expressing solid tumor for which no established therapy exists
* Disease must be measurable by RECIST criteria or evaluable by clinical, radiographic, or laboratory criteria established for the given tumor entity
* Expressing at least one of the following HLA alleles:HLA-A1,-A2,-A3,-A24, and -B7 assessed by HLAgenotyping
* ECOG performance status of ≤1, estimated life expectancy of at least 3 months
* Adequate hematological function defined by WBC ≥3 x 10x9/L, lymphocyte count ≥0.5 x 10x9/L, hemoglobin ≥10 g/dL, platelet count ≥100 x 10x9/L
* Adequate blood coagulation parameters defined as aPTT and INR ≤ 1.5 x ULN
* Adequate renal function defined by a serum creatinine ≤2 x ULN
* Adequate hepatic function defined by total bilirubin ≤2 x ULN and AST and ALT levels ≤2.5 x ULN (in subjects with liver metastases ≤5 x ULN)
* Effective contraception for female and male subjects if the risk of conception exists

Exclusion Criteria:

* Treatment in another clinical study within the past 30 days prior to the first administration of study treatment
* Previous treatment with an investigational anticancer vaccine
* Requirement of concurrent treatment with a nonpermitted drug
* Active significant autoimmune disease (with the exception of vitiligo)
* Receipt of allogeneic stem cell transplantation
* Significant acute or chronic infections (e.g. viral hepatitis, HIV)
* Primary brain tumors and brain metastases (with the exception of brain metastases that are stable after irradiation or surgically resected brain metastases if subjects have been asymptomatic for ≥6 months)
* Rapidly progressive disease (e.g. tumor lysis syndrome)
* Radiotherapy, chemotherapy, surgery (excluding prior diagnostic biopsy), immunotherapy or any investigational drug within 30 days before the start of study treatment
* Pregnancy or lactation
* Active drug or alcohol abuse
* Known hypersensitivity to the study treatment or any of its components
* Any significant disease that, in the Investigator's opinion, should exclude the subject from the study; for questions about this criterion, the Investigator should contact the sponsor.
* Persisting toxicity related to prior therapy ≥grade 2 National Cancer Institute-Common Terminology Criteria For Adverse Events version 3.0
* Legal incapacity or limited legal capacity

Primary outcomes:
measure: To compare 3 doses of EMD 640744 administered by subcutaneous injection in combination with Montanide® ISA 51 VG with regard to immunological efficacy
timeFrame: 1-4 weeks
Secondary outcomes:
measure: To assess the safety and tolerability of different doses of EMD 640744 in Montanide® ISA 51 VG in terms of laboratory parameters and adverse event profile.
timeFrame: 3 months
measure: To assess the clinical efficacy in terms of the overall response, progression-free survival time, and survival time.
timeFrame: 3 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck KGaA, Darmstadt
name: Jens-Peter Marschner, MD
role: STUDY_DIRECTOR
References:
citation: Lennerz V, Gross S, Gallerani E, Sessa C, Mach N, Boehm S, Hess D, von Boehmer L, Knuth A, Ochsenbein AF, Gnad-Vogt U, Zieschang J, Forssmann U, Woelfel T, Kaempgen E. Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors. Cancer Immunol Immunother. 2014 Apr;63(4):381-94. doi: 10.1007/s00262-013-1516-5. Epub 2014 Feb 2.