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

NCT00623831 | Completed Phase 1 Results

• 2 other identifiers: LUD2005-0032006-002015-27
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This was a phase 1, open-label, multiple dose, single-arm study. The mixed bacteria vaccine (MBV) was administered at a starting dose of 250 EU (1 µL) and escalated in each subject to a dose inducing the desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C. The primary objective was to determine the safety profile of MBV in subjects with malignant tumors that expressed the NY-ESO-1 antigen and to identify the dose that induced the desired pyrogenic effect. Secondary objectives were to evaluate the immunological effects and tumor response of subjects following vaccination.

Conditions

Melanoma; Sarcoma; Gastrointestinal Stromal Tumor (GIST); Head and Neck Cancer; Transitional Cell Carcinoma; Prostate Cancer; Ovarian Carcinoma; Esophageal Cancer; Breast Cancer

Keywords

MBV; Mixed Bacterial Vaccine; NY-ESO-1

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 4 weeks after the last dose of study treatment.

  Up to 3 months

• Number of Participants With Pyrogenicity at Each Dose Level Tested in the Intrasubject Dose Escalation Performed Over a Dose Range of 250 to 547,000 EU

  Intrasubject dose escalation performed over a dose range of 250 to 547,000 EU until achievement of the desired pyrogenic effects (i.e., body temperature increase to 38°C to 39.5°C). Of note, the median pyrogenic dose was 60,800 EU.

  Weeks 1 through 6

Secondary Outcomes (2)

• Number of Participants With Serum NY-ESO-1-specific Immune Responses

  Up to 3 months

• Number of Participants With Best Overall Tumor Response

  Up to 3 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

Subjects received MBV at a starting dose of 250 EU (dose level 1) twice weekly, with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed. The maximum possible dose to be investigated was 547,000 EU (dose level 8).

Biological: Mixed bacterial vaccine

Cohort 2

EXPERIMENTAL

Subjects received MBV twice weekly at the fixed dose (60,800 EU \[dose level 6\]) that was determined to be the pyrogenic dose level in Cohort 1.

Biological: Mixed bacterial vaccine

Interventions

Mixed bacterial vaccine BIOLOGICAL

MBV was administered twice weekly by subcutaneous injection in Cohort 1 and by intralesional (preferred) or subcutaneous (if intralesional not possible) injection in Cohort 2. In Cohort 1, the MBV starting dose was 250 EU (dose level 1) with possible intrasubject escalations up to 547,000 EU (dose level 8). In Cohort 2, all subjects received MBV at a fixed dose of 60,800 EU (dose level 6).

Also known as: MBV

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic melanoma, head and neck cancer, transitional cell carcinoma, sarcoma, gastrointestinal stroma tumor (GIST) or prostate cancer.
• Tumor expression of NY-ESO-1 by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry.
• Expected survival of at least 6 months.
• Karnofsky performance status ≥ 70%.
• Fully recovered from surgery.
• Declined, intolerated or completed standard therapy defined as follows 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 - 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.
• Ovarian carcinoma - failure of standard chemotherapy consisting of a platinum agent combined with a taxane and of an anthracycline.
• Esophageal cancer - failure of standard chemotherapy consisting of a platinum agent.
• Breast cancer- failure or intolerance of standard first-, second- and third-line chemotherapy consisting of a taxane and anthracycline. No indication or resistance to standard antihormonal treatment. No indication or resistance to human epidermal growth factor receptor (HER)-2-neu targeted therapy. No indication or resistance to irradiation and/or surgery.

You may not qualify if:

• Clinically significant heart disease (New York Heart Association Class III or IV).
• Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
• Subjects with serious intercurrent illness requiring hospitalization.
• Known human immunodeficiency virus positivity.
• Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of study agent (6 weeks for nitrosoureas).
• Known autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions might have interfered with the evaluation of the induced immune response. Subjects with vitiligo or melanoma-associated hypopigmentation were 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 have compromised 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.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• Krankenhaus Nordwest: collaborator

Study Sites (1)

Krankenhaus Nordwest

Frankfurt, Germany

Location

Related Publications (1)

• Karbach J, Neumann A, Brand K, Wahle C, Siegel E, Maeurer M, Ritter E, Tsuji T, Gnjatic S, Old LJ, Ritter G, Jager E. Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity. Clin Cancer Res. 2012 Oct 1;18(19):5449-59. doi: 10.1158/1078-0432.CCR-12-1116. Epub 2012 Jul 30.

  PMID: 22847809 RESULT

MeSH Terms

Conditions

Melanoma; Sarcoma; Gastrointestinal Stromal Tumors; Head and Neck Neoplasms; Carcinoma, Transitional Cell; Prostatic Neoplasms; Ovarian Neoplasms; Esophageal Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Neoplasms, Female; Endocrine System Diseases; Gonadal Disorders; Esophageal Diseases; Breast Diseases

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

• Elke Jager, MD

  Krankenhaus Nordwest

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2008
• First Posted: February 26, 2008
• Study Start: May 1, 2007
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2013
• Last Updated: October 25, 2022
• Results First Posted: January 9, 2017

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)