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

NCT01580696 | Completed Phase 1

• 1 other identifier: 05-20025/20288
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer; Endometrial Cancer; Fallopian Cancer; Peritoneal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Safety and Local/Systemic Toxicity

  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.

  Duration of the vaccine series

Secondary Outcomes (1)

• Disease-free survival

  Disease-free survival up to 36 months

Study Arms (7)

Non-vaccine clinically matched control group

ACTIVE COMPARATOR

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

E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster

EXPERIMENTAL

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 E39 6 and 12 months after completion of the primary vaccine series.

Biological: E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster

E39 peptide (500mcg) /GM-CSF vaccine plus E39 booster

EXPERIMENTAL

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 E39 6 and 12 months after completion of the primary vaccine series.

Biological: E39 peptide (500mcg)/GM-CSF vaccine plus E39 booster

E39 peptide (1000mcg) /GM-CSF vaccine plus E39 booster

EXPERIMENTAL

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 E39 6 and 12 months after completion of the primary vaccine series.

Biological: E39 peptide (1000mcg)/GM-CSF vaccine plus E39 booster

E39 peptide (100mcg)/GM-CSF vaccine plus J65 booster

EXPERIMENTAL

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 E39' (J65) 6 and 12 months after completion of the primary vaccine series.

Biological: E39 peptide (100mcg)/GM-CSF vaccine plus J65 booster

E39 peptide (500mcg) /GM-CSF vaccine plus J65 booster

EXPERIMENTAL

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 E39' (J65) 6 and 12 months after completion of the primary vaccine series.

Biological: E39 peptide (500mcg)/GM-CSF vaccine plus J65 booster

E39 peptide (1000mcg) /GM-CSF vaccine plus J65 booster

EXPERIMENTAL

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 E39' (J65) 6 and 12 months after completion of the primary vaccine series.

Biological: E39 peptide (1000mcg)/GM-CSF vaccine plus J65 booster

Interventions

E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster BIOLOGICAL

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. Subsequently, patients will receive a booster of E39 dosed at 500mcg and mixed with 250mcg of GM-CSF. The boosters will be given at 6 and 12 months after completing the primary vaccine series above.

Also known as: E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim)

E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster

Non-vaccine clinically matched control group OTHER

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.

Also known as: Clinical tracking for disease progression/recurrence

Non-vaccine clinically matched control group

E39 peptide (500mcg)/GM-CSF vaccine plus E39 booster BIOLOGICAL

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. Subsequently, patients will receive a booster of E39 dosed at 500mcg and mixed with 250mcg of GM-CSF. The boosters will be given at 6 and 12 months after completing the primary vaccine series above.

Also known as: E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim)

E39 peptide (500mcg) /GM-CSF vaccine plus E39 booster

E39 peptide (1000mcg)/GM-CSF vaccine plus E39 booster BIOLOGICAL

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. Subsequently, patients will receive a booster of E39 dosed at 500mcg and mixed with 250mcg of GM-CSF. The boosters will be given at 6 and 12 months after completing the primary vaccine series above.

Also known as: E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim)

E39 peptide (1000mcg) /GM-CSF vaccine plus E39 booster

E39 peptide (100mcg)/GM-CSF vaccine plus J65 booster BIOLOGICAL

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. Subsequently, patients will receive a booster of J65 dosed at 500mcg and mixed with 250mcg of GM-CSF. The boosters will be given at 6 and 12 months after completing the primary vaccine series above.

Also known as: E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim), J65 peptide (an attenuated peptide of E39, EIWTFSTKV)

E39 peptide (100mcg)/GM-CSF vaccine plus J65 booster

E39 peptide (500mcg)/GM-CSF vaccine plus J65 booster BIOLOGICAL

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. Subsequently, patients will receive a booster of J65 dosed at 500mcg and mixed with 250mcg of GM-CSF. The boosters will be given at 6 and 12 months after completing the primary vaccine series above.

Also known as: E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim), J65 peptide (an attenuated peptide of E39, EIWTFSTKV)

E39 peptide (500mcg) /GM-CSF vaccine plus J65 booster

E39 peptide (1000mcg)/GM-CSF vaccine plus J65 booster BIOLOGICAL

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. Subsequently, patients will receive a booster of J65 dosed at 500mcg and mixed with 250mcg of GM-CSF. The boosters will be given at 6 and 12 months after completing the primary vaccine series above.

Also known as: E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim), J65 peptide (an attenuated peptide of E39, EIWTFSTKV)

E39 peptide (1000mcg) /GM-CSF vaccine plus J65 booster

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)
• Ovarian or endometrial, fallopian and peritoneal cancer
• 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)
• Stage I-IV but no evidence of disease (NED) after completion of primary therapies
• Post-menopausal or rendered surgically infertile
• HLA-A2+ patients will receive the vaccine; HLA-A2- patients will be eligible to participate in the control group
• Good performance status (Karnofsky \> 60%, ECOG ≤ 2)
• CBC, CMP, and CA-125 within 2 months of enrollment
• Capable of informed consent

You may not qualify if:

• Patients will be excluded from the study based on the following criteria:
• Receiving immunosuppressive therapy to include chemotherapy, steroids, or methotrexate
• Not post-menopausal or not rendered surgically infertile
• Pregnancy
• In poor health (Karnofsky \< 60%, ECOG \> 2)
• Tbili \> 1.5, creatinine \> 2, hemoglobin \< 10, platelets \< 50,000, WBC \< 2,000
• Active interstitial lung disease; asthma requiring more than as needed bronchodilators for management; or other autoimmune lung disease
• Involved in other experimental protocols (except with permission of the other study PI and completion of the other study dosing regimen)
• History of autoimmune disease

Sponsors & Collaborators

• COL George Peoples, MD, FACS: lead

Study Sites (1)

Mid-Atlantic Gynecologic Oncology & Pelvic Surgery Associates

Annandale, Virginia, 22003, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• John C Elkas, MD, JD

  Mid-Atlantic Gynecologic Oncology & Pelvic Surgical Associates

  PRINCIPAL INVESTIGATOR

• COL George E. Peoples, MD

  Brooke Army Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Surgical Oncology, Brooke Army Medical Center, Director and Principal Investigator, Cancer Vaccine Development Program

Model Details: 3+3 dose escalation study of E39 + GM-CSF in HLA-A2+ patients with HLA-A2- patients followed as a control arm

Study Record Dates

• First Submitted: April 16, 2012
• First Posted: April 19, 2012
• Study Start: April 1, 2012
• Primary Completion: July 31, 2016
• Study Completion: July 31, 2016
• Last Updated: May 4, 2020

Record last verified: 2020-04

Locations

US (1)