Vaccine Therapy in Stage II, III, or IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers
Condition: Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer
MeSH terms: Fallopian Tube Neoplasms
Intervention: ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine; Sargramostim
Intervention description: The vaccine comprises the modified canary pox vector, ALVAC(2), inserted with the following genes: NYESO-1(M), TRICOM (LFA-3, ICAM-1, B7.1), vvE3L, vvK3L. The vaccine is administered at a dose of 0.5 mL SC.; The GM-CSF sargramostim is administered at a dose of 100 μg SC.
Intervention MeSH terms: Sargramostim
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: All patients received the same study treatment.
Masking: None (Open Label)
Enrollment: 13.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent ovarian epithelial cancer; stage II ovarian epithelial cancer; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; fallopian tube cancer; peritoneal cavity cancer

Summary:

      This was a Phase 1, non-randomized, open-label, multicenter study of the
      ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine administered with the granulocyte macrophage-colony
      stimulating factor (GM-CSF) sargramostim in patients with NY-ESO-1- or LAGE-1-positive
      epithelial ovarian, fallopian tube, or primary peritoneal cavity cancers who had completed
      standard therapy for primary or recurrent disease and would have normally entered a period of
      observation. The primary study objective was to determine the safety and tolerability of
      study vaccination, with secondary objectives including the determination of clinical and
      immunological responses.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically documented epithelial carcinoma arising in the ovary, fallopian tube or
             peritoneum, from stage II-IV at diagnosis, treated with initial surgery and
             chemotherapy with at least one platinum-based chemotherapy regimen.

          2. Complete response to frontline therapy as evidenced by negative clinical examination,
             CA-125 tumor marker, and computed tomography (CT) scan. In addition, if second look
             surgery was performed (by laparoscopy or laparotomy), the result must have been either
             negative or microscopic positive. These patients would have normally entered a period
             of observation after standard management.

          3. Patients with recurrent disease were eligible if they had completed surgery and/or
             chemotherapy for recurrent disease and would have normally entered a period of
             observation after completion of standard management. Eligible patients could have had
             asymptomatic residual measurable disease on physical examination and/or CT scan,
             and/or could have had an elevated CA-125 or could have been in complete clinical
             remission (defined as a serum CA-125 ≤ 35 IU/mL, CT scan without objective evidence of
             disease, and normal physical examination).

          4. Tumor expression of 1) NY-ESO-1 by reverse transcription-polymerase chain reaction
             (RT-PCR) (preferably) or immunohistochemistry (IHC); or 2) LAGE-1 by RT-PCR. Patients
             whose primary surgery was performed outside the study site were pre-screened and
             required to release tissue sections or blocks to the study site in order to determine
             tumor expression of NY-ESO-1 by IHC.

          5. Expected survival of at least 6 months.

          6. Full recovery from surgery.

          7. Karnofsky performance status of 70 or more.

          8. Laboratory parameters for vital functions were required to be in the normal range.
             Laboratory abnormalities that were not clinically significant were generally
             permitted, except for the following laboratory parameters, which were required to be
             within the ranges specified:

               -  neutrophil count: ≥ 1.5 × 10^9/L

               -  lymphocyte count: ≥ 0.5 × 10^9/L

               -  platelet count: ≥ 100 × 10^9/L

               -  serum creatinine: ≤ 2 mg/dL

               -  serum bilirubin (total): ≤ 2 mg/dL

               -  hemoglobin: ≥ 10 g/dL

          9. Have been informed of other treatment options.

         10. Age ≥ 18 years.

         11. Able and willing to give valid written informed consent.

        Exclusion criteria:

          1. Metastatic disease to the central nervous system for which other therapeutic options,
             including radiotherapy, may have been available.

          2. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
             disorders).

          3. History of autoimmune disease (e.g., thyroiditis, lupus) except vitiligo.

          4. Other malignancy within 3 years prior to entry into the study, except for treated
             non-melanoma skin cancer and cervical carcinoma in situ.

          5. Known immunodeficiency or human immunodeficiency virus positivity.

          6. Known allergy or history of life-threatening reaction to GM-CSF.

          7. Known allergies to eggs, neomycin, and bovine products, determined by history.

          8. History of severe allergic reactions to vaccines or unknown allergens.

          9. Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or
             transient ischemic attack, chest pain or shortness of breath with activity, or other
             heart conditions being treated by a doctor.

         10. Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to first dosing of study agent.

         11. Mental impairment that could have compromised the ability to give informed consent and
             comply with the requirements of the study.

         12. Lack of availability for immunological and clinical follow-up assessment.

         13. Previous NY-ESO-1 vaccine therapy.