Study of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: NY-ESO-1 ISCOMATRIX® vaccine; Cyclophosphamide
Intervention description: NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.; Cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Cohort 1 was enrolled first, in which subjects received the NY-ESO-1 ISCOM vaccine. Enrollment then proceeded to Cohort 2, in which subjects received the NY-ESO-1 ISCOM vaccine and low-dose cyclophosphamide.
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Clinical Trial; Phase 2; Cancer Vaccine; NY-ESO-1 protein, human; ISCOMATRIX, immunological adjuvant; Cyclophosphamide; T-Cells, Regulatory

Summary:

      This was a Phase 2, open-label study of the NY-ESO-1 ISCOMATRIX® (ISCOM) vaccine administered
      as an intramuscular injection given every 4 weeks to subjects with measurable advanced
      malignant melanoma. Study objectives included determination of the anticancer activity,
      cellular and humoral immunogenicity, and safety and tolerability of the NY-ESO-1 ISCOM
      vaccine administered alone or preceded by a single administration of low-dose
      cyclophosphamide.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Stage IV (metastatic) or unresectable stage III malignant melanoma.

          2. Measurable disease using RECIST.

          3. No other effective therapy available or appropriate.

          4. Expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) or reverse
             transcription-polymerase chain reaction (RT-PCR).

          5. Expected survival of at least 4 months.

          6. Karnofsky performance status of ≥ 70%.

          7. Within 3 weeks prior to first administration of study drug, the following laboratory
             parameters were required to be within the ranges specified:

               -  Hemoglobin ≥ 100 g/L

               -  Platelets ≥ 100 x 10^9/L

               -  International normalized ratio ≤ 2.0

               -  Creatinine ≤ 0.2 mmol/L

               -  Bilirubin ≤ 30 mmol/L

          8. Age ≥ 18 years.

          9. Able and willing to give written informed consent.

        Exclusion Criteria:

          1. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding
             disorders, or any condition that in the opinion of the Investigator would have
             interfered with the ability of the patient to complete all study requirements.

          2. Other malignancy within last 3 years, except for treated melanoma or non-melanoma skin
             cancer or cervical cancer in situ.

          3. Known immunodeficiency.

          4. Known human immunodeficiency virus positivity.

          5. Concomitant systemic treatment with corticosteroids, anti-histaminic drugs, or
             nonsteroidal anti-inflammatory drugs. Specific cyclooxygenase-2 (COX-2) inhibitors,
             low-dose aspirin for the prevention of an acute cardiovascular event, and topical or
             inhaled steroids were permitted.

          6. Chemotherapy and/or radiotherapy within 4 weeks prior to study week 1.

          7. Other immunotherapy within 4 weeks prior to study week 1.

          8. Mental impairment that may have compromised the ability to give informed consent and
             comply with the requirements of the study.

          9. Lack of availability for immunological and clinical follow-up assessment.

         10. Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to enrollment.

         11. Pregnancy or breastfeeding.

         12. Women of childbearing potential: refusal or inability to use effective means of
             contraception.