Therapy for High-Risk HPV 16-Positive Oropharynx Cancer Patients

NCT04001413 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: J1918IRB00179194
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

Combination immune checkpoint inhibitor and DNA vaccine will result in clearance of HPV DNA biomarkers (oral and/or plasma) for patients with persistent HPV-16 E6/E7 DNA (HPV biomarker) after treatment with curative intent.

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma; Oropharynx Cancer; HPV-Related Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of participants in whom there is clearance of Human Papiloma Virus (HPV) biomarkers post-intervention

  Up to 5 years

Secondary Outcomes (2)

• Time to Progression

  Up to 5 years

• Safety of Study Drugs

  Up to 30 days after the last dose of study drug

Other Outcomes (2)

• Clearance of HPV Measured by DNA in participants with HPV E6/E7-specific and MANA-specific T-cell response

  Up to 5 years

• Clearance of HPV Measured by DNA in participants with HPV E6/E7-specific IgG

  Up to 5 years

Study Arms (3)

Arm A: Observational

NO INTERVENTION

No intervention, observational arm.

Arm B: Durvalumab Alone

EXPERIMENTAL

Durvalumab will be administered as an IV Infusion.

Drug: Durvalumab

Arm C: MEDI0457 and Durvalumab

EXPERIMENTAL

MEDI0457 is an injection. Durvalumab will be administered as an IV Infusion.

Drug: MEDI0457; Drug: Durvalumab

Interventions

MEDI0457 DRUG

MEDI0457 is an investigational drug that will be administered with the Cellectra Device in this study

Also known as: INO-3112

Arm C: MEDI0457 and Durvalumab

Durvalumab DRUG

Durvalumab is an investigational drug in this study.

Also known as: MEDI4736

Arm B: Durvalumab Alone; Arm C: MEDI0457 and Durvalumab

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Men and women \>or = 18 years at the time of study entry.
• Histologically or cytologically proven HPV16-positive or p16-positive oropharyngeal squamous cell carcinoma.
• Eastern Cooperative Oncology Group (ECOG) 0-1 (Appendix A)
• Completion of primary therapy curative intent )surgery based or radiation based) within the past year (date of last treatment + 1 year) OR newly diagnosed with a plan for treatment with curative intent OR currently in primary treatment with curative intent.
• Body weight or = 30kg
• Adequate organ function as follows:
• Absolute neutrophil count (ANC) \> or = 1000/mm3
• Platelet count \> or = 75 x 109/L(\> or = 75,000 per mm3)
• Hemoglobin \> or =9 g/dL
• Creatinine \< or = 1.5 x institutional ULN or creatinine clearance (CrCI) \> or = 40mL/min (if using Cockcroft-Gault formula below):
• Female CrCI = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCI= (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
• Total Bilirubin \< or = 1.5 x institutional ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• AST(SGOT)/ALT(SGPT) \< or = 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be \< or = 5x ULN
• Sexually active fertile men must use effective barrier birth control if their partners are WOCBP for up to 217 days after the last dose of durvalumab.

You may not qualify if:

• Participation in another clinical study with an investigational product during or after primary therapy.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Patients with Grade \> or = 2 neuropathy will be evaluated on a case-by-case basis after consultation with Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with Study Physician.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Subjects with a previous diagnosis of another primary malignancy are excluded with the exception of
• Malignancy treated with curative intent and with no known active disease \> or = 3 years and of low potential risk of recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Thyroid or salivary cancer
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]. The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• AstraZeneca: collaborator

Study Sites (4)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Mount Sinai School of Medicine, The Tisch Cancer Institute

New York, New York, 10029, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

MEDI0457; durvalumab

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Carole Fakhry, MD, MPH

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: June 28, 2019
• Study Start: September 17, 2019
• Primary Completion: March 25, 2021
• Study Completion: March 25, 2021
• Last Updated: July 29, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)