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Ovarian CancerPhase 1/2NCT01580696

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

A Phase 1/2 study testing E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster, E39 peptide (500mcg)/GM-CSF vaccine plus E39 booster and E39 peptide (1000mcg)/GM-CSF vaccine plus E39 booster in people with Ovarian Cancer and Endometrial Cancer, run by COL George Peoples, MD, FACS at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster, E39 peptide (500mcg)/GM-CSF vaccine plus E39 booster and E39 peptide (1000mcg)/GM-CSF vaccine plus E39 booster
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
1 siteUnited States
Study dates
Apr 2012to 31 Jul 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • Good performance status (Karnofsky > 60%, ECOG ≤ 2)
  • CBC, CMP, and CA-125 within 2 months of enrollment
  • Capable of informed consent

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Mid-Atlantic Gynecologic Oncology & Pelvic Surgery Associates

    Annandale, Virginia, 22003

Other trials in United States

About this study

Official title: Phase I/IIa Trial of Folate Binding Protein (FBP) Peptide (E39) Vaccine in Ovarian and Endometrial Cancer Patients

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.

Read the detailed description

In this study, investigators intend to assess the safety and document local and systemic toxicity to the folate binding protein (FBP) peptide vaccine E39 + GM-CSF given in the adjuvant setting. Investigators also intend to determine the maximum tolerated dose (MTD) and optimal biologic dose (OBD) for the peptide vaccine, as well as evaluate the in vivo cellular immune response to the vaccine. Time to recurrence in the vaccinated patients vs. matched controls will be tracked.

The primary endpoints are the safety and optimal dosing of the vaccine to induce an in vivo peptide-specific immune response. The clinical endpoint is time to recurrence from date of enrollment.

The study will be a multicenter, phase I/IIa trial of the FBP peptide E39 + GM-CSF. The target study population is female civilian and military health care beneficiaries over the age of 18 years with a diagnosis of ovarian, endometrial, fallopian, or peritoneal cancer who have undergone primary surgical and medical therapies, are post-menopausal or have surgically induced menopause, and are currently without evidence of disease. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA typed since the E39 vaccine is specific for HLA-A2+ patients (approximately 40% of the US population). HLA-A2-patients will be followed as prospective clinically matched controls for recurrence.

HLA-A2+ patients who meet all other eligibility criteria will be tested for biomarkers that indicate progression/recurrence of ovarian and advanced uterine cancer FBP. FBP+ and HLA-A2+ patients will be vaccinated with the FBP peptide (E39) and GM-CSF. HLA-A2-negative patients and those individuals who are eligible to receive the vaccine but who decline will be followed clinically as matched controls for disease recurrence/progression.

Treatment will begin within one month of the subject enrollment in the study and confirmation of eligibility. The 1 ml by volume vaccine will be administered intradermally in 0.5 mL inoculums at two different sites within 5 cm of each other. A total of six vaccinations will be given every 3-4 weeks and will be administered in the same lymph node draining area. The dose escalation scheme is for three patients to receive each of the doses: 100, 500, and 1,000 mcg of peptide. Patients will be enrolled consecutively. An additional three patients may receive a given a dose depending on the presence of dose limiting toxicity (DLT). Prior to the fourth vaccination, each patient will be assessed for liver, renal, and hematopoietic function. If organ function is stable and no DLT is seen, then the patient will continue with the series. After the last patient in a given dose group has completed the third inoculation and organ function is proven stable, then the next dose group will be initiated. Optimal biologic dose (OBD) is defined as the minimum dose of the vaccine that gives the most optimal and lasting in vivo immunologic response to the vaccinated peptide. Up to 15 patients will be vaccinated at the OBD.

Additionally, the E39-vaccinated patients will be randomized to receive either E39 or J65 (an attenuated version of E39) as a booster to promote long-term E39-specific immunity. The clinical endpoints are long-term FBP immunity, time to recurrence from date of enrollment and 5-year survival rate. Those individuals who are eligible to receive the vaccine, but who decline and all HLA-A2- patients will be followed clinically as matched controls for disease recurrence/progression

Subjects will be followed for safety issues, immunologic response and clinical recurrence. Subjects will be monitored 48-72 hours after each inoculation for reaction to the inoculation as well as documentation of any adverse effects experienced. Immunologic response will be documented with both ex vivo phenotypic and functional assays as well as in vivo delayed type hypersensitivity (DTH) reactions. All patients will be followed for a total of 5 years to document disease-free status.

The investigators intend to enroll up to 60 patients will be enrolled study-wide (15-24 in the vaccine arm, up to 36 in the control arm). With accrual beginning in April 2012 enrollment of the last patient is anticipated to occur in December 2014 followed by a five-year follow-up period. The duration of the trial is expected to be seven years.

Being tested
E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster, Non-vaccine clinically matched control group, E39 peptide (500mcg)/GM-CSF vaccine plus E39 booster, E39 peptide (1000mcg)/GM-CSF vaccine plus E39 booster, E39 peptide (100mcg)/GM-CSF vaccine plus J65 booster
Keywords
Folate binding protein, E39 vaccine, Stage I-IV ovarian cancer, Stage I-IV endometrial cancer
Medical subject headings
Ovarian Neoplasms, Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim)

    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.

  • Non-vaccine clinically matched control groupOther

    Also called Clinical tracking for disease progression/recurrence

    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.

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

    Also called E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim)

    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.

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

    Also called E39 peptide (FBP, 191-199, EIWTHSTKV), GM-CSF (sargramostim)

    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.

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

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

    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.

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

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

    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.

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

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

    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.

Study groups in NCT01580696
Study groupRoleWhat they receive
Non-vaccine clinically matched control groupActive comparatorHLA-A2-negative patients and HLA-A2+ patients who decline the vaccine will be followed clinically as matched controls for disease recurrence/progression.
Receives: Other: Non-vaccine clinically matched control group
E39 peptide (100mcg)/GM-CSF vaccine plus E39 boosterExperimentalHLA-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.
Receives: Biological: E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster
E39 peptide (500mcg) /GM-CSF vaccine plus E39 boosterExperimentalHLA-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.
Receives: Biological: E39 peptide (500mcg)/GM-CSF vaccine plus E39 booster
E39 peptide (1000mcg) /GM-CSF vaccine plus E39 boosterExperimentalHLA-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.
Receives: Biological: E39 peptide (1000mcg)/GM-CSF vaccine plus E39 booster
E39 peptide (100mcg)/GM-CSF vaccine plus J65 boosterExperimentalHLA-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.
Receives: Biological: E39 peptide (100mcg)/GM-CSF vaccine plus J65 booster
E39 peptide (500mcg) /GM-CSF vaccine plus J65 boosterExperimentalHLA-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.
Receives: Biological: E39 peptide (500mcg)/GM-CSF vaccine plus J65 booster
E39 peptide (1000mcg) /GM-CSF vaccine plus J65 boosterExperimentalHLA-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.
Receives: Biological: E39 peptide (1000mcg)/GM-CSF vaccine plus J65 booster

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Duration of the vaccine series

Secondary outcomes (1)
  1. Disease-free survival

    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.

    Measured: Disease-free survival up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2012 (estimated)
  2. Study startApr 2012
  3. Primary completion31 Jul 2016
  4. Study completion31 Jul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
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)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01580696
Sponsor's protocol ID
05-20025/20288
Status last verified
Apr 2020
First submitted
16 Apr 2012
Last updated
4 May 2020
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing E39 peptide (100mcg)/GM-CSF vaccine plus E39 booster, E39 peptide (500mcg)/GM-CSF vaccine plus E39 booster and E39 peptide (1000mcg)/GM-CSF vaccine plus E39 booster in people with Ovarian Cancer and Endometrial Cancer, run by COL George Peoples, MD, FACS at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Local/Systemic Toxicity (time frame: Duration of the vaccine series). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2020.

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