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Safety and Efficacy of Ad-p53 in Head and Neck Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03544723
Recruitment Status : Recruiting
First Posted : June 4, 2018
Last Update Posted : March 7, 2019
Information provided by (Responsible Party):
MultiVir, Inc.

Brief Summary:
This is a Phase 2 study of the combination of Ad-p53 administered intra-tumorally with Nivolumab in patients with recurrent head and neck squamous cell cancer and favorable p53 status. There is one cohort consisting of Ad-p53 in combination with Opdivo. Comparison will be made to historical data. General safety and efficacy using RECIST 1.1 and Immune-Related Response Criteria as well as ECOG numbers will be followed.

Condition or disease Intervention/treatment Phase
Recurrent Head and Neck Cancer Drug: Ad-P53 Phase 2

Detailed Description:
This is a Phase 2 study of the combination of Ad-p53 administered intra-tumorally in combination with Opdivo infusions in patients with recurrent head and neck squamous cell cancer and favorable p53 status. This is a safety and efficacy study with one cohort, consisting of the combination of Ad-p53 and monthly infusions of Opdivo. Comparison will be made to historical data. Patients will be followed for adverse events, ECOG status and preliminary efficacy. General safety and preliminary efficacy will be determined using RECIST 1.1, ECOG status and, as indicated, Immune-Related Response Criteria. Biomarker testing of archival or fresh tissue is performed during the study. Patients will undergo a maximum of 3 28-day cycles, with scans every 8 weeks. No additional biopsies will be required after Screening. Enrollment will be up to 20 patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Intervention Model Description: intratumoral Ad-p53 combined with monthly IV Opdivo (nivolumab) infusions
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-Center, Open Label, Randomized Study to Evaluate Efficacy and Safety of Adenoviral p53 (Ad-p53) in Combination With Nivolumab in Patients With Advanced, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC)
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : September 1, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Ad-p53 with Nivolumab 100% of patients
Up to 20 patients, all patients treated with intra-tumoral Ad-P53 3 times week 1 of each cycle, dose determined by tumor size, in combination with IV nivolumab (Opdivo) 480 mg, every 4 weeks, on Day 5 of each Cycle.
Drug: Ad-P53
Antineoplastic, Monoclonal Antibody; PD-1/PD-L1 Inhibitors
Other Names:
  • Opdivo
  • nivolumab

Primary Outcome Measures :
  1. Progression-Free Survival (PFS) of patients using RECIST 1.1 [ Time Frame: Day 1 to progression through end of study, approximately 18 months. ]
    PFS determined by review of scans every 8 weeks for disease progression in accordance with RECIST 1.1. Scans are read locally but kept for possible central review. Scans are done every 8 weeks. Sites will review questionable findings on scans with Immune Related Response Criteria (irRC) [Wolchok 2009].

Secondary Outcome Measures :
  1. Safety assessed by CTCAE [ Time Frame: Screening to 30-days following Final Treatment (approximately 20 weeks) ]
    Incidence of treatment-emergent and treatment-related adverse events (all AEs, laboratory AEs, SAEs and Fatal AEs, in accordance with the CTCAE

  2. Efficacy as determined by biomarker testing and immunohistochemistry testing [ Time Frame: Day 1 of Treatment to End of Study (approximately 18 months) ]
    Efficacy endpoints will be correlated with central biomarker testing for PDL-1, PD-2, as well as central biomarker testing for immune cell infiltrates and tumor mutational burden biomarkers in exploratory analyses, through Cancer Genetics, Inc.

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

Inclusion Criteria:

  1. Signed informed consent.
  2. Male or female * 18 years of age (females of childbearing potential must be non-pregnant, non-lactating). Males and females must agree to use barrier contraception for the duration of the study.
  3. Recurrent head and neck squamous cell carcinoma (HNSCC), excluding endolaryngeal recurrence, meeting the following criteria:

    • Tumor progression after platinum-based chemotherapy
    • HNSCC primary diagnosis must be histologically confirmed.
  4. All lesions should be suitable for ultra-sound guided intra-tumoral injection and the total sum of Ad-p53 Injection Doses (mL) should be less than or equal to 25 mL (see Table 1) as the MTD of Ad-p53 is 2.5x1013 viral particles/treatment day.
  5. Each patient entered on the study must have disease that that is evaluable for response using RECIST 1.1 criteria with a minimum size of 1 cm by CT/MRI or physical examination.
  6. No visible or symptomatic brain metastases
  7. ECOG Performance Status 0-1
  8. Life expectancy > 16 weeks.
  9. Adequate bone marrow and hepatic function as evidenced by the following:

    1. ANC ≥ 1500 cells/mm3
    2. AST/SGOT and/or ALT/SGPT ≤ 3.0 x ULN
    3. alkaline phosphatase ≤ 5 x ULN
  10. Favorable tumor p53 biomarker profile as defined by either wild-type p53 gene configuration by Foundation One CDx assay or <20% p53-positive cells by immunohistochemistry (Nemunaitis 2009). Tumor p53 biomarker evaluations may be performed with tumor tissue (paraffin block or frozen tissue) from either primary or recurrent tumor although samples from recurrence are preferred if both are available. If archival tissue is not available, a fresh tumor biopsy specimen must be evaluated.
  11. Normal troponin blood levels.
  12. Echo with normal ejection fractions.
  13. QTcb ≤ 470 ms
  14. Normal lung oxygen saturation by pulse oximeter.

Exclusion Criteria

  1. History of allergic reactions to any components of the treatments.
  2. Prior radiation performed to areas of measurable disease ≤ four weeks of study entry unless there is documented evidence of disease progression.
  3. Use of systemic anti-cancer therapy ≤ 4 weeks, or six weeks if the systemic therapy contains a nitrosourea or mitomycin C.
  4. Prior additional malignancy within 2 years except for non-melanoma skin cancer, carcinoma in situ of the breast, oral cavity or cervix.
  5. Treatment in clinical studies of non-approved experimental agents ≤ four weeks of study entry.
  6. Prior autologous or allogenic organ or tissue transplantation.
  7. Severe, active comorbidity, including any of the following:

    1. Active clinically serious infection requiring intravenous antibiotics at the time of study entry (CTCAE Grade 2)
    2. Hepatic insufficiency not due to tumor resulting in clinical jaundice or bilirubin > 1.5 x ULN and/or coagulation defects
    3. Thrombotic or embolic event within the last 6 months including portal vein thrombosis
    4. Must not require concomitant treatment with anticoagulants or have an abnormal INR
    5. Bleeding or evidence or history of clinically significant bleeding diathesis or coagulopathy within the last 3 months
    6. Uncontrolled hypertension on anti-hypertensive medication (systolic blood pressure >150 mmHg or diastolic blood pressure >95 mmHg)
    7. Must not have been diagnosed with autoimmune disease or be immunosuppressed
    8. must not have acute or chronic hepatitis B or hepatitis C infection with signs of immunosuppression
    9. Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or immunosuppressive medication including high-dose corticosteroids.
    10. Severe bleeding, hemoptysis, gastrointestinal hemorrhage, CNS bleeding
    11. Clinically significant hemorrhage or vaginal bleeding during the last 6 months
    12. Active brain metastases or leptomeningeal metastases are not allowed
    13. Subjects with active, known or suspected autoimmune disease
    14. Subjects must not have evidence of pneumonitis or inflammatory lung disease on CT scan and chest x-ray.
  8. Chronic treatment for more than 6 months with systemic corticosteroids at doses above 10 mg prednisolone or equivalent before study entry
  9. Psychological, familial, sociological or geographical or other condition which in the opinion of the investigator would not permit study follow-up or other compliance with the study protocol.
  10. Subjects may not have tumors adjacent to vital structures such as carotid arteries.

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 identifier (NCT number): NCT03544723

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Contact: Beatha H Sellman, MA 713-668-5684
Contact: Kerstin B Menander, MD PhD 713-665-9058

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United States, Ohio
University of Toledo Dana Cancer Center Recruiting
Toledo, Ohio, United States, 43614
Sponsors and Collaborators
MultiVir, Inc.

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Responsible Party: MultiVir, Inc. Identifier: NCT03544723     History of Changes
Other Study ID Numbers: Ad-p53-002
First Posted: June 4, 2018    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Journal articles and posters, no identifiable data

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents