NCT02275039

Brief Summary

This phase I trial studies the side effects and recommended dose of the combination of p53MVA vaccine (modified vaccinia virus ankara vaccine expressing tumor protein p53 \[p53\]) and gemcitabine hydrochloride in treating patients with ovarian epithelial cancer that has come back. Vaccines made from inserting a laboratory-treated gene into a person's tumor cells may help the body build an effective immune response to kill tumor cells that express p53. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving modified vaccinia virus ankara vaccine expressing p53 together with gemcitabine hydrochloride may work better in treating patients with ovarian epithelial cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2015

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 23, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 27, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

January 1, 2015

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 23, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 23, 2018

Completed
Last Updated

April 30, 2018

Status Verified

April 1, 2018

Enrollment Period

3.3 years

First QC Date

October 23, 2014

Last Update Submit

April 26, 2018

Conditions

Recurrent Ovarian Epithelial CancerRecurrent Fallopian Tube CarcinomaRecurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

  • Recommended dose for the combination of gemcitabine hydrochloride and modified vaccinia virus ankara vaccine expressing p53

    The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be used to grade adverse events. To be evaluable for toxicity, a patient must have received one course of gemcitabine and modified vaccinia virus ankara vaccine expressing p53 or experienced a dose-limiting toxicity.

    Up to 42 days (2 courses)

Secondary Outcomes (2)

  • Clinical responses, assessed by modified RECIST criteria

    Up to 12 months

  • Changes in T cell reactivity to p53

    Baseline to up to 52 weeks

Study Arms (1)

Treatment (MVA-p53 vaccine and gemcitabine hydrochloride)

EXPERIMENTAL

Patients receive modified vaccinia virus ankara vaccine expressing p53 SC on day 15 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then continue to receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: modified vaccinia virus ankara vaccine expressing p53Drug: gemcitabine hydrochlorideOther: laboratory biomarker analysis

Interventions

modified vaccinia virus ankara vaccine expressing p53BIOLOGICAL

Given SC

Also known as: MVA-p53 vaccine, MVAp53 vaccine
Treatment (MVA-p53 vaccine and gemcitabine hydrochloride)
gemcitabine hydrochlorideDRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Treatment (MVA-p53 vaccine and gemcitabine hydrochloride)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (MVA-p53 vaccine and gemcitabine hydrochloride)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with histologically or cytologically confirmed, epithelial ovarian, primary peritoneal or fallopian tube cancer who experienced recurrence or progression within 12 months after completion of platinum based chemotherapy; patients must have measurable disease or detectable disease:
  • Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be greater than or equal to 10 mm when measured by computerized tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI); lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT, PET/CT or MRI
  • Detectable disease in a patient is defined as one who does not have measurable disease, but has at least one of the following conditions:
  • Baseline values of cancer antigen-125 (CA-125) at least 2 x upper limit of normal (ULN)
  • Ascites and/or pleural effusion attributed to tumor
  • Solid and/or cystic abnormalities on radiographic imaging that do not meet modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria, immune-related response criteria (irRC) for target lesions
  • Patients whose ovarian cancer recurs/progresses within 0-6 months following platinum-based chemotherapy have platinum resistant disease; such patients are eligible for this trial
  • Patients with documented disease recurrence/progression within 6-12 months of completing platinum-based therapy, are considered to have 'borderline' platinum sensitivity; these patients are eligible for this trial if agreed by the patient and the treating physician
  • Patients who relapse more than 12 months after completion of platinum-based treatment are considered 'platinum sensitive' and will not be eligible for this trial
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
  • Patients must have a life expectancy of at least 3 months
  • Absolute neutrophil count \>= 1,500/ul
  • Platelets \>= 100,000/ul; low platelet counts may be corrected with transfusion to achieve eligibility for study
  • The hemoglobin level must be greater than 9 g/dL; low hemoglobin counts may be corrected with transfusion to achieve eligibility for study
  • Calculated or measured creatinine clearance \>= 50 ml/min or serum creatinine =\< 1.6 mg/dl
  • +8 more criteria

You may not qualify if:

  • Patients should not have any uncontrolled illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • No other malignancy is allowed except for the following: adequately treated basal or squamous cell carcinoma, superficial bladder cancer, any carcinoma in situ or any other cancer from which the patient has been disease free for at least 3 years
  • Patients may not be receiving any additional investigational agents or radiation therapy
  • History of severe environmental allergies or allergy to egg proteins
  • Pregnant women are excluded from this study
  • Patients with known brain metastases will be excluded
  • Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients with a family history or Li-Fraumeni syndrome will not be eligible
  • Concurrent use of corticosteroids (exceptions: nasal corticosteroids, inhaled steroids, adrenal replacement steroids and steroid creams are allowed)
  • Patients with a history of immunodeficiency, including organ grafts and human immunodeficiency virus (HIV), will not be eligible
  • Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
  • Patients with any active autoimmune disease or a condition that requires systemic corticosteroids or other immunosuppressive medications will be excluded; exceptions to this are subjects with vitiligo, type I diabetes mellitus and autoimmune thyroiditis only requiring hormone replacement, who will be permitted to enroll

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Carcinoma, Ovarian EpithelialFallopian Tube Neoplasms

Interventions

MVAp53 vaccineGemcitabine

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsOvarian NeoplasmsEndocrine Gland NeoplasmsNeoplasms by SiteOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersFallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Mihaela Cristea

    City of Hope Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 23, 2014

First Posted

October 27, 2014

Study Start

January 1, 2015

Primary Completion

April 23, 2018

Study Completion

April 23, 2018

Last Updated

April 30, 2018

Record last verified: 2018-04

Locations

US(1)