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A Randomized Pilot Trial of Consolidation With an Adjuvant Ovarian Cancer Vaccine Oregovomab (Ovarex ®) With/Without Single-Dose Cyclophosphamide After a Complete Clinical Response to Second-Line Taxane/Platinum-Based Therapy to Determine Immune Response and Time to Progression in Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma


N/A
18 Years
N/A
Not Enrolling
Both
Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

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Trial Information

A Randomized Pilot Trial of Consolidation With an Adjuvant Ovarian Cancer Vaccine Oregovomab (Ovarex ®) With/Without Single-Dose Cyclophosphamide After a Complete Clinical Response to Second-Line Taxane/Platinum-Based Therapy to Determine Immune Response and Time to Progression in Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma


OBJECTIVES:

Primary

- To characterize the nonspecific humoral immune response, as measured by human
anti-murine antibodies (HAMA), in patients with stage III or IV ovarian epithelial,
fallopian tube, or primary peritoneal adenocarcinoma treated with consolidation therapy
comprising adjuvant oregovomab with vs without cyclophosphamide after achieving a
complete clinical response to second-line taxane/platinum-based therapy.

- To compare the magnitude of the immune responses in these patients at approximately 14
weeks after the initial treatment.

- To determine the frequency and severity of adverse events, as assessed by NCI CTCAE
v3.0, in patients treated with these regimens.

Secondary

- To characterize the specific humoral immune response, as measured by HAMA and
anti-idiotype antibodies, in these patients.

- To assess the treatment emergent cellular immune response, by measuring the
delayed-type hypersensitivity response to the anergy panel and to oregovomab as
compared to baseline, in these patients.

- To characterize the duration of each patient's first progression-free interval after
primary chemotherapy and second progression-free interval after another regimen of
chemotherapy.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients undergo delayed-type hypersensitivity (DTH) skin testing with
oregovomab and a standard anergy panel (i.e., mumps, Candida, and tetanus toxoid) on
day 0 (at baseline) and at week 14. The skin test response is measured 48 hours later.
Patients receive cyclophosphamide IV on day 6 and oregovomab IV over 20 minutes on day
9 or 10. Patients then receive oregovomab alone at weeks 6 and 10 and then every 12
weeks for up to 2 years (10 doses) in the absence of disease progression or
unacceptable toxicity.

- Arm II: Patients undergo DTH skin testing and receive oregovomab as in arm I. Blood
samples are obtained from patients at baseline and at weeks 14 and 38 for immunologic
correlative studies. Samples are examined to determine CA-125 levels and human
anti-murine antibody (HAMA) and anti-idiotype antibody levels by enzyme-linked
immunosorbent assay (ELISA).

After completion of study therapy, patients are followed every 3 months for 2 years and then
every 6 months for 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal
adenocarcinoma

- Histologic documentation of the original primary tumor is required via pathology
report

- FIGO stage III-IV disease

- Must have received 5-8 courses of front-line taxane- and platinum-based chemotherapy
OR treatment on a first-line Gynecologic Oncology Group (GOG) protocol AND must have
become clinically free of disease as measured by serum CA-125 level, CT scan, or
physical examination

- Must have documentation of a defined progression-free interval after front-line
therapy, as measured from the date of initiation of front-line chemotherapy to
the date of initiation of second-line chemotherapy

- Relapsed disease (prior to starting second-line chemotherapy), defined by 1 of the
following:

- Doubling of serum CA-125 level confirmed by measurements taken 1 week apart

- CA-125 level should have been elevated to at least double the level seen
during the first complete response

- Identification of a new lesion by CT/MRI scan or physical examination

- Must have completed 5-8 courses of second-line taxane- and platinum-based
chemotherapy 4-8 weeks ago

- Second-line chemotherapy must not have been started before clear evidence of
disease recurrence was documented using RECIST criteria

- Achieved complete clinical response to second-line chemotherapy with no symptoms
suggestive of persistent disease, defined by the following:

- Normal physical examination

- Reduction from the peak serum CA-125 level to a normal value of ≥ 5 U/mL

- Complete regression of recurrent lesions by CT scan of the abdomen/pelvis

- No low malignant potential tumors or noninvasive disease

PATIENT CHARACTERISTICS:

- GOG performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.0 g/dL

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- AST ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- No active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus
erythematosus, ulcerative colitis, Crohn's disease, multiple sclerosis, or ankylosing
spondylitis)

- No known allergy to murine proteins, documented anaphylactic reaction to any drug, or
intolerance to cyclophosphamide

- No recognized immunodeficiency disease, including cellular immunodeficiencies,
hypogammaglobulinemia, or dysgammaglobulinemia

- No acquired, hereditary, or congenital immunodeficiencies

- No other concurrent uncontrolled diseases

- No contraindications to pressor agents

- No other invasive malignancies within the past 5 years, except nonmelanoma skin
cancer

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior cancer treatment that would contraindicate study therapy

- No concurrent chronic treatment with immunosuppressive drugs (e.g., cyclosporine,
adrenocorticotropic hormone [ACTH], or systemic corticosteroids)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Serum human anti-murine antibodies (HAMA) as assessed by enzyme-linked immunosorbent assay (ELISA) at approximately 14 weeks after initial treatment

Safety Issue:

No

Principal Investigator

Robert P. Edwards, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Pittsburgh

Authority:

United States: Federal Government

Study ID:

CDR0000570624

NCT ID:

NCT00551265

Start Date:

October 2007

Completion Date:

Related Keywords:

  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Primary Peritoneal Cavity Cancer
  • stage III ovarian epithelial cancer
  • stage IV ovarian epithelial cancer
  • recurrent ovarian epithelial cancer
  • fallopian tube cancer
  • primary peritoneal cavity cancer
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial

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