Phase Ib Trial of Two Folate Binding Protein Peptide Vaccines (E39 and J65) in Breast and Ovarian Cancer Patients

NCT02019524 | Completed Phase 1 DMC

• 1 other identifier: 2013-0139
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, single-blinded, three-arm phase Ib study of the folate binding protein vaccines E39 and J65. The study target population are patients with breast or ovarian cancer diagnosis who have been treated and are without evidence of disease. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA typed. E39 and J65 are cytotoxic T-lymphocyte-eliciting peptide vaccines that are restricted to HLA-A2+ patients (approximately 50% of the U.S. population).

Conditions

Breast Cancer; Ovarian Cancer

Keywords

Stage I breast cancer; Stage II breast cancer; Stage IIIA, IIIB, and IIIC breast cancer; Male breast cancer; Ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Primary vaccination strategy

  Determine which of the following primary vaccination strategy maximizes long-term specific immunity defined as E39-specific cytotoxic T lymphocytes (CTLs) six months following completion of the primary vaccination series.

  Six months after completion of primary vaccination series (month 12 of trial)

Secondary Outcomes (3)

• Short-term immunity

  One month after completion of primary vaccination series (month 7 of trial)

• Optimal booster inoculation strategy

  Twelve months after completion of primary vaccination series (month 18 of trial)

• Delayed Type Hypersensitivity evaluation

  Baseline to six months after completion of primary vaccination series (month 18 of trial)

Study Arms (3)

E39 peptide vaccine

EXPERIMENTAL

Patients receive 6 monthly injections of E39 peptide + GM-CSF. Immunologic data is assessed at 1 month and 6 months (+/- 2 weeks) after the primary vaccine series (PVS), specifically ex vivo immunologic recognition of E39 and J65 is assessed by clonal expansion using a dextramer assay and the in vivo response is assessed by delayed type hypersensitivity. The 6-month post-PVS immunologic data is then used to assess each patient for significant residual immunity. Patients are then sorted into two groups: those with SRI and those without. Patients within each group will be randomized to receive 1 booster inoculation of the J65 vaccine or the E39 vaccine. Patients return to the clinic within 1-2 weeks of their 6-month post-PVS visit to receive their booster inoculation.

Biological: E39 peptide vaccine

E39 vaccine then J65 vaccine

EXPERIMENTAL

Patients receive 3 inoculations with the E39 vaccine followed by 3 inoculations with the J65 vaccine. Immunologic data is assessed at 1 month and 6 months (+/- 2 weeks) after the primary vaccine series (PVS), specifically ex vivo immunologic recognition of E39 and J65 is assessed by clonal expansion using a dextramer assay and the in vivo response is assessed by delayed type hypersensitivity. The 6-month post-PVS immunologic data is then used to assess each patient for significant residual immunity. Patients are then sorted into two groups: those with SRI and those without. Patients within each group will be randomized to receive 1 booster inoculation of the J65 vaccine or the E39 vaccine. Patients return to the clinic within 1-2 weeks of their 6-month post-PVS visit to receive their booster inoculation.

Biological: E39 vaccine then J65 vaccine

J65 vaccine then E39 vaccine

EXPERIMENTAL

Patients receive 3 inoculations with the J65 vaccine followed by 3 inoculations with the E39 vaccine. Immunologic data is assessed at 1 month and 6 months (+/- 2 weeks) after the primary vaccine series (PVS), specifically ex vivo immunologic recognition of E39 and J65 is assessed by clonal expansion using a dextramer assay and the in vivo response is assessed by delayed type hypersensitivity. The 6-month post-PVS immunologic data is then used to assess each patient for significant residual immunity. Patients are then sorted into two groups: those with SRI and those without. Patients within each group will be randomized to receive 1 booster inoculation of the J65 vaccine or the E39 vaccine. Patients return to the clinic within 1-2 weeks of their 6-month post-PVS visit to receive their booster inoculation.

Biological: J65 vaccine then E39 vaccine

Interventions

E39 peptide vaccine BIOLOGICAL

500mcg of lyophilized E39 peptide is suspended in bacteriostatic saline for injection and then frozen. At the time of vaccine administration, one vial of frozen suspended peptide is thawed and mixed with 250mcg GM-CSF in the syringe. This constitutes the E39 peptide vaccine. For patients randomized to the E39 vaccine arm, the primary vaccine series (PVS) consists of E39 vaccine administered intradermally every three to four weeks for six total vaccinations. After completion of the PVS, patients are assessed for significant residual immunity (SRI). Patients with SRI will be randomized to receive one inoculation of either the E39 vaccine or the J65 vaccine. Patients without SRI will be randomized to receive one inoculation of either the E39 vaccine or the J65 vaccine.

Also known as: E39 peptide (EIWTHSYKV, Folate Binding Protein, 191-199), GM-CSF (Sargramostim)

E39 peptide vaccine

E39 vaccine then J65 vaccine BIOLOGICAL

The E39 vaccine is prepared as noted above. For the J65 vaccine, 500mcg J65 peptide is suspended in bacteriostatic saline for injection and then frozen. At the time of vaccine administration, one vial of frozen suspended E39 peptide is thawed and mixed with 250mcg GM-CSF in the syringe. This constitutes the J65 vaccine. For patients randomized to this arm, the primary vaccine series (PVS) consists of the E39 vaccine administered intradermally every 3-4 weeks for 3 total vaccinations. Patients are then administered the J65 vaccine every 3-4 weeks for a total of 3 vaccinations. After completion of the PVS, patients are assessed for significant residual immunity (SRI). Patients with SRI will be randomized to receive 1 inoculation of either the E39 vaccine or the J65 vaccine. Patients without SRI will be randomized to receive 1 inoculation of either the E39 vaccine or the J65 vaccine.

Also known as: J65 peptide (EIWTFSTKV, Folate Binding Protein), GM-CSF (Sargramostim), E39 peptide (EIWTHSYKV, Folate Binding Protein, 191-199)

E39 vaccine then J65 vaccine

J65 vaccine then E39 vaccine BIOLOGICAL

The E39 and J65 vaccines are prepared as noted above. For patients randomized to this arm, the primary vaccine series (PVS) consists of the J65 vaccine administered intradermally every 3-4 weeks for 3 total vaccinations. Patients are then administered the E39 vaccine every 3-4 weeks for a total of 3 vaccinations. After completion of the PVS, patients are assessed for significant residual immunity (SRI). Patients with SRI will be randomized to receive 1 inoculation of either the E39 vaccine or the J65 vaccine. Patients without SRI will be randomized to receive 1 inoculation of either the E39 vaccine or the J65 vaccine.

Also known as: J65 peptide (EIWTFSTKV, Folate Binding Protein), GM-CSF (Sargramostim), E39 peptide (EIWTHSYKV, Folate Binding Protein, 191-199)

J65 vaccine then E39 vaccine

Eligibility Criteria

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

You may qualify if:

• Patients must have breast or ovarian cancer
• Patients must have completed primary breast or ovarian cancer therapy (i.e., surgery, chemotherapy, immunotherapy and/or radiation therapy as appropriate per standard of care for patient's specific cancer)
• Patients must be without evidence of residual disease as assessed by their treatment team
• Patients must be either post-menopausal or surgically post-menopausal
• Patients must be HLA-A2 positive
• Patients must have a good performance status (ECOG\<2)

You may not qualify if:

• HLA-A2 negative patients
• Currently receiving immunosuppressive therapy to include chemotherapy, steroids, or methotrexate
• In poor health (Karnofsky \<60%, ECOG \>2)
• Total bilirubin \>1.5, creatinine \>2, hemoglobin \<10, platelets \<50,000, WBC \<2,000
• Active pulmonary disease requiring medication to include multiple inhalers
• Of child-bearing age with intact reproductive organs
• Involved in other experimental protocols (except with permission of the other study PI)
• History of autoimmune disease

Sponsors & Collaborators

• COL George Peoples, MD, FACS: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Vreeland TJ, Litton JK, Qiao N, Philips AV, Alatrash G, Hale DF, Jackson DO, Peace KM, Greene JM, Berry JS, Clifton GT, Peoples GE, Mittendorf EA. Phase Ib trial of folate binding protein (FBP)-derived peptide vaccines, E39 and an attenuated version, E39': An analysis of safety and immune response. Clin Immunol. 2018 Jul;192:6-13. doi: 10.1016/j.clim.2018.03.010. Epub 2018 Mar 21.

  PMID: 29574039 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Breast Neoplasms, Male

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland 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

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

• Elizabeth Mittendorf, MD

  Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Cancer Vaccine Development Program/Chief, Surgical Oncology, Brooke Army Medical Center

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 24, 2013
• Study Start: September 30, 2013
• Primary Completion: December 6, 2016
• Study Completion: December 6, 2016
• Last Updated: March 18, 2020

Record last verified: 2020-03

Locations

US (1)