Phase 1
Completed N=17
A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen
Source: ClinicalTrials.gov NCT00623831 ↗Enrolled (actual)
17
Serious AEs
11.8%
Results posted
Jan 2017
Primary outcomePrimary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) — 13; 4; 3; 2 participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
13; 4; 3; 2; 0; 0 | — |
| PRIMARY 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 |
1; 1; 1; 1; 2; 2 | — |
| SECONDARY Number of Participants With Serum NY-ESO-1-specific Immune Responses |
9; 2; 1; 5; 6; 1 | — |
| SECONDARY Number of Participants With Best Overall Tumor Response |
2; 1; 1; 0; 0; 1 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
- Within the last 2 weeks prior to study day 1, vital laboratory parameters must have been within the normal range, except for the following laboratory parameters, which must have been within the ranges specified:
- Absolute neutrophil count (ANC): ≥ 1,000/mm3
- Platelet count: ≥ 75,000/mm3
- Alanine aminotransferase (ALT): ≤ 5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST): ≤ 5 x ULN
- Total bilirubin: ≤ 2.5 x ULN
- Creatinine: ≤ 2 mg/dL
- Age ≥ 18 years.
- Able and willing to give written informed consent.
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT00623831). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.