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BRIEF TITLE: Study of a p53MVA Vaccine in Combination With Pembrolizumab

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


  • Org Study ID: 15002
  • Secondary ID: NCI-2015-00653,15002
  • NCT ID: NCT02432963
  • NCT Alias:
  • Sponsor: City of Hope Medical Center - Other
  • Source: City of Hope Medical Center

Brief Summary

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.

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.

Overal Status Start Date Phase Study Type
Recruiting Start Date: November 17, 2015 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: 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

Primary Outcome 1 - Time Frame: Up to week 20

Condition:

  • Adult Solid Neoplasm
  • Bladder Carcinoma
  • Colon Carcinoma
  • Estrogen Receptor Negative
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • HER2/Neu Negative
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
  • Progesterone Receptor Negative
  • Rectal Carcinoma
  • Renal Cell Carcinoma
  • Soft Tissue Sarcoma
  • Triple-Negative Breast Carcinoma
  • TP53 Gene Mutation
  • Unresectable Solid Neoplasm

Eligibility

Criteria:
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
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Vincent Chung

Role: Principal Investigator

Affiliation: City of Hope Medical Center

Location

Facility Status Contact
City of Hope Medical Center
Duarte, California 91010
United States
Recruiting Vincent Chung
800-826-4673