A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen
Condition: Melanoma; Sarcoma; Gastrointestinal Stromal Tumor (GIST); Head and Neck Cancer; Transitional Cell Carcinoma; Prostate Cancer; Ovarian Carcinoma; Esophageal Cancer; Breast Cancer
MeSH terms: Carcinoma; Gastrointestinal Stromal Tumors; Carcinoma, Transitional Cell
Intervention: Mixed bacterial vaccine
Intervention description: 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).
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MBV; Mixed Bacterial Vaccine; NY-ESO-1

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed metastatic melanoma, head and neck cancer, transitional cell
             carcinoma, sarcoma, gastrointestinal stroma tumor (GIST) or prostate cancer.

          2. Tumor expression of NY-ESO-1 by reverse transcriptase and polymerase chain reaction
             (RT-PCR) analysis, preferably, or immunohistochemistry.

          3. Expected survival of at least 6 months.

          4. Karnofsky performance status ≥ 70%.

          5. Fully recovered from surgery.

          6. Declined, intolerated or completed standard therapy defined as follows for each tumor
             entity:

               1. Melanoma - resistance or intolerance to dacarbazine.

               2. Sarcoma - resistance or intolerance to anthracyclines and to one
                  platinum-containing chemotherapy regimen, no indication for irradiation.

               3. GIST - failure or intolerance of imatinib and sunitinib.

               4. Head and neck cancer - no indication for irradiation, resistance or intolerance
                  to platinum-containing chemotherapy.

               5. Transitional cell carcinoma - resistance or intolerance to cisplatin combined
                  with gemcitabine.

               6. Prostate cancer- failure of antihormonal treatment and resistance or intolerance
                  to docetaxel.

               7. Ovarian carcinoma - failure of standard chemotherapy consisting of a platinum
                  agent combined with a taxane and of an anthracycline.

               8. Esophageal cancer - failure of standard chemotherapy consisting of a platinum
                  agent.

               9. 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.

          7. 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

          8. Age ≥ 18 years.

          9. Able and willing to give written informed consent.

        Exclusion Criteria:

          1. Clinically significant heart disease (New York Heart Association Class III or IV).

          2. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding
             disorders.

          3. Subjects with serious intercurrent illness requiring hospitalization.

          4. Known human immunodeficiency virus positivity.

          5. Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of
             study agent (6 weeks for nitrosoureas).

          6. 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.

          7. Chronic use of immunosuppressive drugs such as systemic corticosteroids.

          8. Other malignancy within 3 years prior to entry into the study, except for treated
             non-melanoma skin cancer and cervical carcinoma in situ.

          9. Mental impairment that may have compromised the ability to give informed consent and
             comply with the requirements of the study.

         10. Lack of availability for immunological and clinical follow-up assessments.

         11. Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to first dosing of study agent.

         12. Pregnancy or breastfeeding.

         13. Women of childbearing potential: Refusal or inability to use effective means of
             contraception.