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ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer

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ClinicalTrials.gov Identifier: NCT02002182
Recruitment Status : Recruiting
First Posted : December 5, 2013
Last Update Posted : March 21, 2019
Sponsor:
Collaborator:
Advaxis, Inc.
Information provided by (Responsible Party):
Andrew Sikora, Baylor College of Medicine

Brief Summary:

Some cancers may be related to an infection with a virus, such as the Human Papilloma Virus (HPV). HPV related Oropharyngeal cancer (HPVOPC) accounts for 80% of oropharynx cancer cases in the United States. HPVOPC has better prognosis than patients with HPV negative oropharynx cancer. In many hospitals, the standard of care treatment for oropharyngeal cancer is surgery and/or radiotherapy with or without chemotherapy. While chances of survival for most patients with HPVOPC is very good, current treatments are associated with short- and long-term side effects which can be severe. In pre-clinical research using animal models of cancer, vaccination targeting the HPV virus has been found to cause tumor regression. Thus, approaches which target the unique characteristics of HPV-infected cancer cells, such as therapeutic vaccination, are attractive strategies for potentially reducing radiotherapy and chemo radiotherapy regimens (and thus decreasing toxicity) and enhancing long-term disease control.

The purpose of this study is to see if an experimental vaccine, ADXS11-001, is effective in stimulating the body's defense system against HPV-positive oropharyngeal squamous cell carcinoma before transoral (through the mouth) surgery. The experimental product ADXS11-001 uses a live strain of the Listeria monocytogenes (Lm) bacteria that has been genetically modified such that the risk of getting an infection is significantly reduced. Several research studies have already been conducted with ADXS11-001 in men and women with cancer. So far, approximately 722 doses of ADXS11-001 have been given to 290 patients with HPV associated cancers.


Condition or disease Intervention/treatment Phase
Head and Neck Cancer Squamous Cell Carcinoma of the Head and Neck HPV Positive Oropharyngeal Squamous Cell Carcinoma Biological: ADXS11-001 (ADXS-HPV) Phase 2

Detailed Description:

This is an investigator-initiated prospective clinical study of patients with stage I-IV squamous cell carcinoma of the oropharynx (OPSCC) who are to undergo ablative transoral robotic surgery (TORS).

There is a vaccination group and a control group in this study.

Subjects in the control group will not receive the vaccination and will only be followed after TORS surgery for additional research blood tests to measure how their immune system is working.

Subjects in the vaccination group will receive two vaccinations prior to surgery. The first dose will be about 33 days before surgery, and the second will be about 14 days before surgery.

Participation in this study will also include allowing the research team to take several blood samples from the subject at various times before, during, and after treatment for his/her cancer.

Vaccination subjects will be monitored closely after treatment and includes 6 months of oral antibiotics.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Window of Opportunity Trial of Neoadjuvant ADXS 11-001 Vaccination Prior to Robot -Assisted Resection of HPV-Positive Oropharyngeal Squamous Cell Carcinoma
Study Start Date : December 2013
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment-Vaccine Group
Two vaccinations with ADXS11-001 (ADXS-HPV) will be given at a dose of 1x10^9 cfu intravenously. The drug will be given as a 500ml infusion over 60 minutes.
Biological: ADXS11-001 (ADXS-HPV)
ADXS11-001 (ADXS-HPV) is a live attenuated Listeria monocytogenes (Lm)-LLO immunotherapy developed for the treatment of HPV-associated dysplasia and malignancy.
Other Names:
  • ADXS11-001
  • ADXS-HPV

No Intervention: Control Group
Observational control group treated with standard of care therapy only



Primary Outcome Measures :
  1. Change in HPV E6/E7-specific CD8+ cytotoxic lymphocyte (CTL) responses [ Time Frame: Baseline and Day 25 ]
    The primary endpoint will be the change in HPV E6/E7-specific CD8+ cytotoxic lymphocyte (CTL) responses in the peripheral blood at time of surgery, with respect to baseline.

  2. Degree of ADX11-001 toxicity [ Time Frame: Baseline ]
    NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria, with any grade 3 or 4 toxicity considered as an adverse outcome.

  3. Degree of ADX11-001 toxicity [ Time Frame: Day 15 ]
    NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria, with any grade 3 or 4 toxicity considered as an adverse outcome.

  4. Degree of ADX11-001 toxicity [ Time Frame: Day 25 ]
    NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria, with any grade 3 or 4 toxicity considered as an adverse outcome.


Secondary Outcome Measures :
  1. Vaccine induced HPV E6/E7specific CD8+ CTL responses [ Time Frame: Baseline and 3 weeks ]
    Vaccine induced HPV E6/E7specific CD8+ CTL responses in the blood 3 weeks after surgery, with respect to baseline levels, in vaccinated patients and unvaccinated controls.

  2. Vaccine induced HPV E6/E7specific CD8+ CTL responses [ Time Frame: Baseline and 6 weeks ]
    Vaccine induced HPV E6/E7specific CD8+ CTL responses in the blood 6 weeks after surgery, with respect to baseline levels, in vaccinated patients and unvaccinated controls.

  3. Vaccine induced HPV E6/E7specific CD8+ CTL responses [ Time Frame: Baseline and 3 months ]
    Vaccine induced HPV E6/E7specific CD8+ CTL responses in the blood 3 months after surgery, with respect to baseline levels, in vaccinated patients and unvaccinated controls.

  4. Vaccine induced HPV E6/E7specific CD8+ CTL responses [ Time Frame: Baseline and 6 months ]
    Vaccine induced HPV E6/E7specific CD8+ CTL responses in the blood 6 months after surgery, with respect to baseline levels, in vaccinated patients and unvaccinated controls.

  5. Vaccine induced HPV E6/E7specific CD8+ CTL responses [ Time Frame: Baseline and 12 months ]
    Vaccine induced HPV E6/E7specific CD8+ CTL responses in the blood 12 months after surgery, with respect to baseline levels, in vaccinated patients and unvaccinated controls.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has newly-diagnosed, biopsy proven squamous cell carcinoma of Stage I-IV (T1-3, N0-2b) of the oropharynx.
  • The patient's tumor is HPV positive by PCR or ISH assay of tumor biopsy.
  • The patient is able/eligible to undergo treatment with transoral robotic surgery (TORS) with or without neck dissection and with or without adjuvant radiation therapy or chemoradiation.
  • The patient is able to understand and give informed consent.
  • The patient is at least 18 years old.
  • The patient's ECOG performance status is </= 2.

Exclusion Criteria:

  • The patient has had prior head and neck squamous cell carcinoma (HNSCC), with the exception of superficial cutaneous basal cell or squamous cell carcinomas.
  • The patient has active cancer in another part of the body, with the exception of superficial cutaneous basal cell or squamous cell carcinomas
  • If a cancer survivor, the disease free interval is less than 3 years, with the exception of superficial cutaneous basal cell or squamous cell carcinomas.
  • If a cancer survivor the patient received prior systemic chemotherapy or radiotherapy
  • If prior standard-of-care pre-treatment biopsy is inadequate for analysis by immunohistochemistry, and the patient is unwilling to undergo an additional biopsy procedure.
  • The patient is a prisoner.
  • The patient has a psychiatric illness or developmental delay which would interfere with understanding of the study and provision of informed consent.
  • The patient has previously received definitive surgical, radiation, or chemoradiation treatment for HNSCC.
  • The patient has a history of HIV or other known cause of immunosuppression, or is actively taking immunosuppressive medications due to organ transplantation, rheumatoid disease, or other medical conditions.
  • Patient is allergic to naproxen or Ibuprofen.
  • The patient has a history of liver disease.
  • The patient has a contraindication (e.g. sensitivity/allergy) to both trimethoprim/sulfamethoxazole and ampicillin.
  • The patient has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants and venous access devices (e.g. Port-a-Cath or Mediport) are permitted.
  • Patients who are receiving or may receive future treatment with PI3K or TNFα inhibitors.
  • Patients who have undergone a major surgery, including surgery for a new artificial implant and/or device, within 6 weeks prior to the initiation of ADXS11-001 treatment. Sponsor must be consulted prior to enrolling subjects on the study who recently had a major surgery or have new artificial implant, and/or devices.
  • Patients who have a history of listeriosis or prior ADXS11-001 therapy.
  • Patients with a known allergy to any component of the study treatment formulations.
  • Pregnancy. The effects of this vaccine on the developing human fetus are unknown. For this reason women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02002182


Contacts
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Contact: Yesenia Ramirez 713-798-8541 yramirez@bcm.edu

Locations
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United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Brett Miles, MD       brett.miles@mountsinai.org   
Contact: Alex Park, MD    (212) 241-4282    Alex.park@mountsinai.org   
Principal Investigator: Brett Miles, MD         
United States, Texas
Baylor College of Medicine Not yet recruiting
Houston, Texas, United States, 77030
Contact: Anita Sabichi, MD    713-798-3750    sabichi@bcm.edu   
Sponsors and Collaborators
Andrew Sikora
Advaxis, Inc.
Investigators
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Study Chair: Andrew G Sikora, MD PhD Baylor College of Medicine
Principal Investigator: Brett Miles, MD Icahn School of Medicine at Mount Sinai

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Responsible Party: Andrew Sikora, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02002182     History of Changes
Other Study ID Numbers: GCO 13-1411
First Posted: December 5, 2013    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019

Keywords provided by Andrew Sikora, Baylor College of Medicine:
HPV
oropharynx
squamous cell carcinoma
head and neck cancer
transoral robotic surgery

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Vaccines
Immunologic Factors
Physiological Effects of Drugs