Vaccine Therapy in Treating Patients With Metastatic Solid Tumors

NCT01376505 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-09138NCI-2011-00920
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of vaccine therapy in treating patients with metastatic solid tumors. Vaccines made from antibodies and peptides combined with tumor cells may help the body build an effective immune response to kill tumor cells.

Conditions

Malignant Solid Tumour; Breast Cancer; Malignant Tumor of Colon; GIST; Ovarian Cancer

Keywords

Vaccine Therapy

Outcome Measures

Primary Outcomes (2)

• Type and duration of immune response measured over time to repeat vaccine administration

  Immune response will be defined by Enzyme-linked immunosorbent assay (ELISA), Flow cytometry, T-cell proliferation and cytokine. The magnitude of antibody levels will be assessed to the vaccine and HER-2 over-expressing cells (e.g.,BT474). Lymphoproliferative responses will be assessed by a non radioactive cell proliferation assay Bioplex human isotyping kit will be used to assess antibody types and cytokine profiles.

  up to 6 months

• Clinical benefit will be assessed

  Will re-evaluate disease status with tumor markers and RESIST criteria,or full evaluation upon development of new symptoms

  up to 6 months

Secondary Outcomes (1)

• Evaluation of safety and toxicity at regular intervals by NCI common toxicity criteria (CTCAE v 4.0)

  up to 6 months

Study Arms (2)

HER-2 Vaccine

EXPERIMENTAL

combination of MVF-HER-2 (597-626) and MVF-HER-2 (266-296) emulsified with nor-MDP and ISA 720 This escalation arm has completed. The trial has moved on to the extension arm

Biological: HER-2 vaccine

EXTENSION HER-2 Vaccine at OBD

EXPERIMENTAL

Combination of MVF-HER-2 (597-626) and MVF-HER-2 (266-296) emulsified with nor-MDP and ISA 720 at dose level cohort 2 This extension arm is ongoing

Biological: Extension HER-2 vaccine trial at OBD

Interventions

HER-2 vaccine BIOLOGICAL

Three intramuscular (IM) injections (separated by 21 days) of a mixture of two peptides {MVF-HER-2(597-626) and MVF-HER-2 (266-296)} vaccine emulsified with nor-MDP in ISA 720 vehicle. Increasing doses of the combined vaccine preparation emulsified with nor-MDP (0.025) mg and Montanide ISA 720 will be administered in a final volume of 1.0 ml. Starting at dose level 1, 1.0mg of each peptide will be used for vaccination. In increasing dosing cohorts 1.5mg, 2.0mg and 2.5mg will be used. Patients may also receive 6 months booster shots.

Also known as: Synthetic peptides of HER-2 comprising B cell epitopes with a Promiscuous T cell epitope of Measles Virus.

HER-2 Vaccine

Extension HER-2 vaccine trial at OBD BIOLOGICAL

Three intramuscular (IM) injections (separated by 21 days) of a mixture of two peptides {MVF-HER-2(597-626) and MVF-HER-2 (266-296)} vaccine emulsified with nor-MDP in ISA 720 vehicle. The dose level has been determined to be cohort 2. The combined vaccine preparation consists of 1.5mg of each of the HER-2 vaccine emulsified with nor-MDP (0.025) mg and Montanide ISA 720 will be administered in a final volume of 1.0 ml. Patients may also receive 6 months booster shots.

EXTENSION HER-2 Vaccine at OBD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have histologically confirmed metastatic solid tumor; the malignancy should be considered incurable using standard treatment
• Patients are not required to have HER-2 over-expression to be on this study
• If the patient has had HER-2 expression measured prior to enrollment, the report alone will be accepted
• If the patient has not had HER-2 expression measured prior to enrollment on this study tumor tissue blocks and/or freshly isolated tissue must be available for determination of HER-2 expression
• Patients are not required to have epidermal growth factor receptor (EGFR) over-expression to be on this study
• If the patient has had EGFR expression measured prior to enrollment, the report alone will be accepted
• If the patient has not had EGFR expression measured prior to enrollment on this study tumor tissue blocks and/or freshly isolated tissue must be available for determination of EGFR expression
• Patients with prior history of treated brain metastases who are off steroids and have stable metastatic brain disease for at least 3 months are eligible
• Patients must be ambulatory with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• White blood cells \> 3500/mm\^3
• Platelet count \> 100,000/mm\^3
• Serum bilirubin \< 1.5 mg %, regardless of whether patients have liver involvement secondary to tumor
• Alanine aminotransferase (ALT) must be \< 2 times upper limit of normal
• Creatinine \< 1.5 mg/dL or calculated creatinine clearance \> 60 mL/min
• Patients will be tested for reactivity to a panel of four common microbial skin test antigens: candida, trichophyton, intermediate strength purified protein derivative (PPD), and tetanus toxoid; determination of patient eligibility for this trial will proceed independently of these skin test results; patients who have previously been tested for these antigens but were excluded from participation in the trial due to non-reactivity may be considered as eligible provided that all other eligibility criteria are met

You may not qualify if:

• Patients with ICH of 0
• Patients on targeted therapies, such as Cycline Dependent Kinase (CDK) 4/6 or mammalian target of rapamycin (mTOR) inhibitors in combination with endocrine therapy.
• Patients who are {MVF-HER-2(266-296) and MVF-HER-2 (597-626)} immediate hypersensitivity skin test positive
• Patients who have evidence of active infection that requires antibiotic therapy; patients must have been off antibiotic treatment for at least 3 weeks prior to initiating treatment and must be confirmed to be clear of the infection; if patient develops an infection requiring antibiotic treatment while on the treatment portion of the study patients will be treated for the active infection with antibiotics and will resume vaccine treatment when the infection is healed
• Patients with known active human immunodeficiency virus (HIV), hepatitis A, hepatitis B, or hepatitis C infection
• Patients with serious cardiopulmonary disorders, including congestive heart failure, symptomatic coronary artery disease, serious cardiac arrhythmia, and symptomatic chronic obstructive pulmonary disease or patients with other serious uncontrolled medical diseases
• Patients who require or likely to require corticosteroids or other immunosuppressives for intercurrent disease are NOT eligible
• Splenectomized patients
• Autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis dermatomyositis, or a vasculitic syndrome
• Patients who have developed anaphylactic responses to other vaccines
• History of congestive heart failure, coronary artery disease and myocardial infarction; active or unstable cardiovascular disease or cardiac disease requiring drug or device intervention
• ADDITIONAL KEY ELIGIBILITY CRITERIA FOR EXTENSION \& EXPANSION COHORT:
• Histologically documented metastatic or unresectable breast, ovarian and gastrointestinal cancers
• Progressive disease after at least one line of standard therapy
• Patients must have received or refused first line standard systemic therapy for their metastases (if applicable)

Sponsors & Collaborators

• Robert Wesolowski: lead

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Bekaii-Saab T, Wesolowski R, Ahn DH, Wu C, Mortazavi A, Lustberg M, Ramaswamy B, Fowler J, Wei L, Overholser J, Kaumaya PTP. Phase I Immunotherapy Trial with Two Chimeric HER-2 B-Cell Peptide Vaccines Emulsified in Montanide ISA 720VG and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors. Clin Cancer Res. 2019 Jun 15;25(12):3495-3507. doi: 10.1158/1078-0432.CCR-18-3997. Epub 2019 Feb 25.

  PMID: 30804020 BACKGROUND

Related Links

• Jamesline

MeSH Terms

Conditions

Breast Neoplasms; Colonic Neoplasms; Ovarian Neoplasms

Interventions

CHP-HER2 vaccine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Robert Wesolowski, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 9, 2011
• First Posted: June 20, 2011
• Study Start: June 21, 2011
• Primary Completion: November 28, 2022
• Study Completion: November 28, 2022
• Last Updated: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)