Phase I/IIa Trial of Folate Binding Protein Vaccine in Ovarian Cancer

• Sponsor: COL George Peoples, MD, FACS
• Information provided by (Responsible Party): COL George Peoples, MD, FACS, San Antonio Military Medical Center

Study Description

Brief Summary:

Folate binding protein (FBP) is highly over-expressed in breast, ovarian and endometrial cancers and is the source of immunogenic peptides (E39) that can stimulate cytotoxic T lymphocytes (CTL) to recognize and destroy FBP-expressing cancer cells in the laboratory. The purpose of this study is to test whether a peptide-based vaccine consisting of the E39 peptide mixed with the FDA-approved immunoadjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) is safe and effective at inducing an in vivo peptide-specific immune response. Furthermore, the investigators intend to determine the best dose of the vaccine to utilize to produce this immunity most efficiently. The investigators will determine whether immunity to FBP will prevent clinical recurrence. Additionally, the investigators will compare these results with results from a trial utilizing the E75 peptide (from the HER2/neu protein) in ovarian and endometrial cancer patients in preparation for studying a combination vaccine.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Endometrial Cancer; Fallopian Cancer; Peritoneal Cancer	Biological: E39 peptide (100mg)/GM-CSF vaccine; Other: Non-vaccine clinically matched control group; Biological: E39 peptide (500mg)/GM-CSF vaccine; Biological: E39 peptide (1000mg)/GM-CSF vaccine	Phase 1; Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	51 participants
Allocation:	Randomized
Intervention Model:	Sequential Assignment
Intervention Model Description:	3+3 dose escalation study of E39 + GM-CSF in HLA-A2+ patients with HLA-A2- patients followed as a control arm
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase I/IIa Trial of Folate Binding Protein (FBP) Peptide (E39) Vaccine in Ovarian and Endometrial Cancer Patients
Study Start Date :	April 2012
Actual Primary Completion Date :	July 31, 2016
Actual Study Completion Date :	July 31, 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Non-vaccine clinically matched control group; HLA-A2-negative patients and HLA-A2+ patients who decline the vaccine will be followed clinically as matched controls for disease recurrence/progression.	Other: Non-vaccine clinically matched control group; HLA-A2-negative patients or HLA-A2-positive patients who decline the vaccine will be followed clinically as matched controls for disease recurrence/progression. No experimental treatment will be administered to this group.; Other Name: Clinical tracking for disease progression/recurrence
Experimental: E39 peptide (100mg)/GM-CSF vaccine; HLA-A2+ patients receive 100mg E39 peptide/GM-CSF vaccine intradermally every 3-4 weeks for a total of up to six inoculations followed by 500mg booster inoculations of either E39 or E39' (J65) 6 and 12 months after completion of the primary vaccine series.	Biological: E39 peptide (100mg)/GM-CSF vaccine; 100mcg lyophilized E39 peptide is suspended in bacteriostatic water for injection in individual cryovials and frozen. At the time of vaccine administration, the suspended peptide is thawed and mixed thoroughly with 250mcg GM-CSF in the syringe. This constitutes the E39 vaccine at this dose; Other Names: E39 peptide (FBP, 191-199, EIWTHSTKV); GM-CSF (sargramostim)
Experimental: E39 peptide (500mg) /GM-CSF vaccine; HLA-A2+ patients receive 500mg E39 peptide/GM-CSF vaccine intradermally every 3-4 weeks for a total of up to six inoculations followed by 500mg booster inoculations of either E39 or E39' (J65) 6 and 12 months after completion of the primary vaccine series.	Biological: E39 peptide (500mg)/GM-CSF vaccine; 500mcg lyophilized E39 peptide is suspended in bacteriostatic water for injection in individual cryovials and frozen. At the time of vaccine administration, the suspended peptide is thawed and mixed thoroughly with 250mcg GM-CSF in the syringe. This constitutes the E39 vaccine at this dose; Other Names: E39 peptide (FBP, 191-199, EIWTHSTKV); GM-CSF (sargramostim)
Experimental: E39 peptide (1000mg) /GM-CSF vaccine; HLA-A2+ patients receive 1000mg E39 peptide/GM-CSF vaccine intradermally every 3-4 weeks for a total of up to six inoculations followed by 500mg booster inoculations of either E39 or E39' (J65) 6 and 12 months after completion of the primary vaccine series.	Biological: E39 peptide (1000mg)/GM-CSF vaccine; 1000mcg lyophilized E39 peptide is suspended in bacteriostatic water for injection in individual cryovials and frozen. At the time of vaccine administration, the suspended peptide is thawed and mixed thoroughly with 250mcg GM-CSF in the syringe. This constitutes the E39 vaccine at this dose; Other Names: E39 peptide (FBP, 191-199, EIWTHSTKV); GM-CSF (sargramostim)

Outcome Measures

Primary Outcome Measures :

1. Safety and Local/Systemic Toxicity [ Time Frame: Duration of the vaccine series ]
   Standard local and systemic toxicities will be collected and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events, v4.03 toxicity scale. For the vaccine series (one vaccine/month for six months), patients will be monitored closely for one hour after vaccine inoculation with questioning, serial exams and vital signs every 15 minutes to observe for a hypersensitivity reaction. Patients will also return to the clinic 48-72 hours after each inoculation for questioning regarding systemic toxicity and to examine and measure inoculation site local reactions.

Secondary Outcome Measures :

1. Disease-free survival [ Time Frame: Disease-free survival up to 36 months ]
   Disease-free survival (DFS) for all patients regardless of randomization will be determined by the patients' own physicians at the individual study sites during routine follow-up screening. This will occur every three months for the first 24 months after diagnosis and then every six months for an additional 36 months.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients will be included in the study based on the following criteria. (Enrollment may commence 1 month from completion of standard primary therapies and up to two years after completion of treatment.)

1. Ovarian or endometrial, fallopian and peritoneal cancer
2. Completion of primary first-line therapies (i.e., surgery, chemotherapy, immunotherapy and radiation therapy as appropriate per standard of care for patient's specific cancer)
3. Stage I-IV but no evidence of disease (NED) after completion of primary therapies
4. Post-menopausal or rendered surgically infertile
5. HLA-A2+ patients will receive the vaccine; HLA-A2- patients will be eligible to participate in the control group
6. Good performance status (Karnofsky > 60%, ECOG ≤ 2)
7. CBC, CMP, and CA-125 within 2 months of enrollment
8. Capable of informed consent

Exclusion Criteria:

Patients will be excluded from the study based on the following criteria:

1. Receiving immunosuppressive therapy to include chemotherapy, steroids, or methotrexate
2. Not post-menopausal or not rendered surgically infertile
3. Pregnancy
4. In poor health (Karnofsky < 60%, ECOG > 2)
5. Tbili > 1.5, creatinine > 2, hemoglobin < 10, platelets < 50,000, WBC < 2,000
6. Active interstitial lung disease; asthma requiring more than as needed bronchodilators for management; or other autoimmune lung disease
7. Involved in other experimental protocols (except with permission of the other study PI and completion of the other study dosing regimen)
8. History of autoimmune disease

Contacts and Locations

Locations

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United States, Virginia
Mid-Atlantic Gynecologic Oncology & Pelvic Surgery Associates
Annandale, Virginia, United States, 22003

Sponsors and Collaborators

COL George Peoples, MD, FACS

Investigators

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Principal Investigator:	John C Elkas, MD, JD	Mid-Atlantic Gynecologic Oncology & Pelvic Surgical Associates
Study Director:	COL George E. Peoples, MD	Brooke Army Medical Center

More Information

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Responsible Party:	COL George Peoples, MD, FACS, Chief, Surgical Oncology, Brooke Army Medical Center, Director and Principal Investigator, Cancer Vaccine Development Program, San Antonio Military Medical Center
ClinicalTrials.gov Identifier:	NCT01580696 History of Changes
Other Study ID Numbers:	05-20025/20288
First Posted:	April 19, 2012
Last Update Posted:	May 7, 2018
Last Verified:	April 2018

Keywords provided by COL George Peoples, MD, FACS, San Antonio Military Medical Center:

Folate binding protein; E39 vaccine; Stage I-IV ovarian cancer; Stage I-IV endometrial cancer

Additional relevant MeSH terms:

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Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endometrial Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial	Neoplasms by Histologic Type; Uterine Neoplasms; Uterine Diseases; Vaccines; Sargramostim; Folic Acid; Vitamin B Complex; Immunologic Factors; Physiological Effects of Drugs; Hematinics; Vitamins; Micronutrients; Nutrients; Growth Substances