Coley's Toxins - CLINICAL TRIAL FRANKFURT

A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Active	18 and over	Other	LUD2005-003 EudraCT:2006-002015-27, NCT00623831

Trial Description

Summary

This is a phase 1, open label, multiple dosing, single arm study. Each patient will be enrolled to receive MBV subcutaneously at the starting dose of 250 EU (1 µL) twice weekly. In the absence of a dose-limiting toxicity (DLT, the MBV dose will be escalated in each patient to the MBV dose level that elicits a body temperature of 38C -39.5C or up to the maximum dose level 8. Once the desired pyrogenic effect is reached, patients will then be given MBV twice weekly for 4 doses at the pyrogenic dose level. For patients not achieving the desired pyrogenic effect at dose level 8, no additional MBV will be administered.Vaccination will be administered twice weekly on Monday and Thursday of each week.

During each vaccination clinic visit, patients will be observed up to 6 hours post vaccination and vital signs will be measured hourly. At baseline, and throughout the study period, patients will be assessed for NY-ESO-1 specific humoral and cellular immunity, chemistry, hematology and cytokine analysis for IL-1, IL-6, IFNgamma, and TNF-alpha. Toxicity assessments will be made throughout the study.

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed metastatic melanoma, head and neck cancer, transitional cell carcinoma, sarcoma, GIST (gastrointestinal stroma tumor) or prostate cancer

• Tumor expression of 1) NY-ESO-1 by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis (see Appendix 1), preferably, or immunohistochemistry (20);

• Expected survival of at least 6 months.

• Karnofsky performance scale >/-70 %.

• Fully recovered from surgery.

• Declined, intolerated or completed standard therapy defined as following for each tumor entity:

• Melanoma- Resistance or intolerance to Dacarbazine.

• Sarcoma-Resistance or intolerance to Anthracyclines and to one Platinum containing chemotherapy regimen, no indication for irradiation.

• GIST (gastrointestinal stroma tumor)- Failure or intolerance of Imatinib and Sunitinib

• Head and Neck Cancer -No indication for irradiation, resistance or intolerance to platinum containing chemotherapy.

• Transitional Cell Carcinoma - Resistance or intolerance to Cisplatin combined with Gemcitabine

• Prostate Cancer- Failure of antihormonal treatment and resistance or intolerance to Docetaxel

• Within the last 2 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified:

• Absolute neutrophil count (ANC) >/- 1,000/mm3

• Platelets >/-75,000/mm3

• Creatinine </- 2 mg/dL

• ALT, AST </- 5 x ULN

• Alk Phos and total bilirubin </- 2.5 x ULN

• Age ≥ 18 years

• Able and willing to give valid written informed consent

Exclusion Criteria:

• Clinically significant heart disease (NYHA Class III or IV).

• Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.

• Patients with serious intercurrent illness, requiring hospitalization.

• Known HIV positivity

• Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of study agent (6 weeks for nitrosoureas).

• Known autoimmune disease (RA, SLE), as these conditions might interfere with the evaluation of the induced immune response. Patients with vitiligo or melanoma-associated hypopigmentation are not excluded.

• Chronic use of immunosuppressive drugs such as systemic corticosteroids.

• Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.

• Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.

• Lack of availability for immunological and clinical follow-up assessments.

• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study agent.

• Pregnancy or breastfeeding.

• Women of childbearing potential: Refusal or inability to use effective means of contraception.

Trial Contact Information

Trial Lead Organizations/Sponsors

Ludwig Institute for Cancer Research

Elke Jaeger

Principal Investigator

Antje Neumann		Ph: 069 7601-4161
		Email: neumann.antje@khnw.de

Trial Sites

Germany
	Frankfurt
	Krankenhaus Nordwest
		Antje Neumann	Ph: 069 7601 4161
			Email: neumann.antje@khnw.de
		Elke Jaeger	Principal Investigator
		Eckhart Weidmann, MD	Sub-Investigator
		Armin Bender, MD	Sub-Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00623831
Information obtained from ClinicalTrials.gov on April 05, 2010

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.