Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy

March 18, 2024 updated by: City of Hope Medical Center

A Phase I Study of a p53MVA Vaccine in Combination With Pembrolizumab

This phase I trial studies the side effects of vaccine therapy and pembrolizumab in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment, that have failed prior therapy, and that cannot be removed by surgery. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving vaccine therapy together with pembrolizumab may be a better treatment in patients with solid tumors.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of combined p53MVA vaccine (modified vaccinia virus Ankara vaccine expressing p53) and pembrolizumab that are well-tolerated in patients with refractory, tumor protein 53 (p53) over expressing cancer.

SECONDARY OBJECTIVES:

I. To evaluate clinical response and anti-p53 T cell immune responses.

OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes followed by modified vaccinia virus Ankara vaccine expressing p53 subcutaneously (SC) at least 30 minutes later once in weeks 1, 4, and 7.

Patients may receive additional doses of pembrolizumab in weeks 10, 13, 16, and 19, for a maximum of 7 doses if there are no signs of progressive disease. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Since p53 mutations occur in a wide variety of tumor types, this is a mixed histology study for incurable tumors; subjects with the following solid tumors are eligible for screening: non-small cell lung cancer, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, renal cell carcinoma, melanoma, bladder, soft tissue sarcoma, triple-negative breast cancer, and colorectal carcinoma displaying microsatellite instability and pancreatic cancer
  • Advanced (unresectable) solid tumors: patients must have failed or been intolerant to at least one line of standard therapy or refuse standard treatment
  • Performance status: patients must have an Eastern Cooperative Oncology Group (ECOG) =< 2 (Karnofsky >= 60%)
  • Informed consent: all subjects must have the ability to understand and the willingness to sign an Institutional Review Board (IRB) approved consent form
  • Absolute neutrophil count: >= 1,500/ul
  • Platelets >= 100,000/ul
  • Hemoglobin level: must be greater than 9 g/dL
  • Renal function: calculated or measured creatinine clearance >= 50 ml/min and/or serum creatinine =< 1.6 mg/dl
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times institutional upper normal level (AST and ALT =< 5 times institutional upper normal level, if there is evidence of liver metastasis)
  • Confirmed p53 involvement: patients with p53 over-expression by immunohistochemistry (>= 10% of cells within the tumor staining positive) or those with a p53 mutation as determined by mutational analysis of tumor tissue will be eligible; patients with prior exposure to p53-based vaccines will be eligible
  • Agreement to use adequate contraception: women of child-bearing potential must use contraception prior to study entry and for six months after study participation; men that are sexually active whose partners are women of childbearing age must use condoms

Exclusion Criteria:

  • Patients may not be receiving any additional investigational agents or radiation therapy
  • Pregnancy: pregnant women are excluded from this study; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately; women who are pregnant or breastfeeding are excluded
  • Patients with known brain metastasis
  • Radiotherapy within 4 weeks prior to entering the study
  • Patients with previous exposure to anti-programmed cell death (PD)-1 or anti-programmed cell death ligand 1 (PDL-1) will not be eligible
  • History of allergy to egg proteins
  • Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Concurrent use of systemic corticosteroids (nasal corticosteroids, inhaled steroids, adrenal replacement steroids, and topical steroids are allowed)
  • History of immunodeficiency or autoimmune disease: patients with a history of immunodeficiency, including organ grafts and human immunodeficiency virus (HIV), will not be eligible
  • Patients with a history of autoimmune disease will also be excluded, specifically those with any active autoimmune disease or a condition that requires systemic corticosteroids; exceptions to this are subjects with vitiligo and type I diabetes mellitus, who will be permitted to enroll
  • Patients with a history of severe immune-mediated adverse reactions with ipilimumab: this will be defined as any grade 4 toxicity requiring treatment with corticosteroids (greater than 10 mg/day prednisone or equivalent dose) for greater than 12 weeks
  • Patients with a history of cardiac disease are excluded; baseline electrocardiography and assessment of serum troponin (I) are included the screening exams; subjects in whom these assays are abnormal (electrocardiogram [EKG] excluding 1st degree bundle branch block, sinus bradycardia, sinus tachycardia or non-specific T wave changes, serum troponin >= grade 2) are ineligible
  • Non-compliance: if it is the opinion of the investigator that a subject may be unable to comply with the safety monitoring requirements of the study, they will be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (p53MVA, pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes followed by modified vaccinia virus Ankara vaccine expressing p53 SC at least 30 minutes later once in weeks 1, 4, and 7. Patients may receive additional doses of pembrolizumab in weeks 10, 13, 16, and 19, for a maximum of 7 doses if there are no signs of progressive disease. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • MK-3475
  • Lambrolizumab
  • SCH 900475
Biological: Modified Vaccinia Virus Ankara Vaccine Expressing p53
Given SC
Other Names:
  • MVA-p53 Vaccine
  • MVAp53 Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Tolerability of combined modified vaccinia virus Ankara vaccine expressing p53 and pembrolizumab, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.3
Time Frame: Up to week 20
Up to week 20

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical responses, assessed by the modified Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Up to week 19
Evaluated using immune-related response criteria (irRECIST, irRC).
Up to week 19
T cell reactivity to p53, assessed by flow cytometry
Time Frame: Up to week 19
Immunosuppressive cell types (MDSC, Tregs) and other selected lymphocyte subsets and markers including PD-1, PDL-1 and PDL-2 will be quantified. The Wilcoxon rank-sum test will be used, and are based on residual re-sampling simulations based on historical AUC values (subtracting baseline) and a hypothesized increase in that AUC.
Up to week 19

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Vincent Chung, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 14, 2016

Primary Completion (Actual)

December 4, 2017

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

April 29, 2015

First Submitted That Met QC Criteria

May 1, 2015

First Posted (Estimated)

May 4, 2015

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 18, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15002 (Other Identifier: City of Hope Medical Center)
  • NCI-2015-00653 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma

Clinical Trials on Laboratory Biomarker Analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Togo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe