Neoplasms

All Conditions

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

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Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Vaccines

Immunologic Factors

Antimetabolites

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.

modified vaccinia virus ankara vaccine expressing p53

gemcitabine hydrochloride

laboratory biomarker analysis

Mihaela Cristea

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.

PRIMARY OBJECTIVES:

I. To determine a recommended dose for the combination of a p53MVA vaccine and gemcitabine (gemcitabine hydrochloride) and if it is well-tolerated in patients with platinum resistant, p53 over expressing ovarian cancer.

SECONDARY OBJECTIVES:

I. To evaluate T cell immunity changes and clinical response.

OUTLINE:

Patients receive modified vaccinia virus ankara vaccine expressing p53 subcutaneously (SC) on day 15 and gemcitabine hydrochloride intravenously (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.

After completion of study treatment, patients are followed up for 12 months.

p53MVA Vaccine and Gemcitabine Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer

A Phase I Study of a p53MVA Vaccine in Combination With Gemcitabine in Ovarian Cancer

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.

Peripheral blood samples will be collected pre- and post-immunization for assessment of anti-p53 T cell responses and immunophenotyping. Immunosuppressive cell types (myeloid derived suppressor cells, regulatory T cells) and other selected lymphocyte subsets and markers including programmed cell death protein 1, programmed death-ligand 1 (PDL-1) and PDL-2 will be quantified.

National Cancer Institute (NCI)

City of Hope Medical Center

Fallopian Tube Neoplasms

Fallopian Tube Diseases

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pembrolizumab IV over 30 minutes every 3 weeks and modified vaccinia virus ankara vaccine expressing p53 SC every 3 weeks for up to 3 vaccines. Cycles with pembrolizumab repeat every 3 weeks for up to 49 weeks in the absence of disease progression or unacceptable toxicity.

Modified Vaccinia Virus Ankara Vaccine Expressing p53

Thanh Dellinger

This phase II trial studies how well modified vaccinia virus ankara vaccine expressing p53 (p53MVA) and pembrolizumab work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving p53MVA and pembrolizumab together may work better in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

PRIMARY OBJECTIVE:

I. To assess response rate (complete responses and partial responses) after treatment with p53MVA and pembrolizumab.

SECONDARY OBJECTIVE:

I. To assess median progression free survival (PFS), clinical benefit (complete response, partial response lasting \> 6 months), overall survival (OS), safety and tolerability.

EXPLORATORY OBJECTIVE:

I. Evaluate if the CD8+ T cell signal exceeds that detected in the single agent p53MVA trial.

OUTLINE: This is a dose-escalation study of modified vaccinia virus ankara vaccine expressing p53.

Patients receive pembrolizumab intravenously (IV) over 30 minutes every 3 weeks and modified vaccinia virus ankara vaccine expressing p53 subcutaneously (SC) every 3 weeks for up to 3 vaccines. Cycles with pembrolizumab repeat every 3 weeks for up to 49 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1-3 weeks and every 12 weeks thereafter.

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Clinical benefit will be calculated as the % of patients experiencing CR or PR or SD in total. Will be summarized by PDL-1 expression.

Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.3.

Peripheral blood samples will be collected pre- and post-immunization for assessment of anti-p53 T cell responses and immunophenotyping. Immunosuppressive cell types (myeloid-derived suppressor cell, regulatory T cells) and other selected lymphocyte subsets and markers including PD-1, PDL-1 and PDL-2 will be quantified. Will evaluate if CD8+ T cell signal exceeds that detected in the single agent p53MVA trial. Estimates will be obtained using Wilcoxon rank-sum test based on residual re-sampling simulations based on historic area under the curve values.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
p53MVA Vaccine and Gemcitabine Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer	NCT02275039	Recurrent Ovari... Recurrent Fallo... Recurrent Prima...	modified vaccin... gemcitabine hyd... laboratory biom...	18 Years -	City of Hope Medical Center
p53MVA Vaccine and Gemcitabine Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer	NCT02275039	Recurrent Ovari... Recurrent Fallo... Recurrent Prima...	modified vaccin... gemcitabine hyd... laboratory biom...	18 Years -	City of Hope Medical Center
P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer	NCT03113487	Recurrent Plati... Recurrent Plati... Recurrent Plati...	Modified Vaccin... Pembrolizumab	18 Years -	City of Hope Medical Center
p53MVA Vaccine and Gemcitabine Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer	NCT02275039	Recurrent Ovari... Recurrent Fallo... Recurrent Prima...	modified vaccin... gemcitabine hyd... laboratory biom...	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for modified vaccinia virus ankara vaccine expressing p53