Hemopurifier Plus Pembrolizumab in Head and Neck Cancer

NCT04453046 | Terminated DMC FDA Device

• 1 other identifier: AEMD-2019-01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is an Early Feasibility Study (EFS) investigating the use of the Hemopurifier to clear immunosuppressive exosomes in combination with pembrolizumab (Keytruda) in the front line setting, in patients with advanced and/or metastatic squamous cell carcinoma of the head and neck.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Head- Neck Cancer; Hemopurifier; Pembrolizumab; Keytruda; Exosome; Immuno-oncology; Checkpoint inhibitor

Outcome Measures

Primary Outcomes (2)

• Safety as measured by adverse events

  Safety will be determined in an Early Feasibility Phase I clinical trial for patients with recurrent/metastatic HNSCC who will undergo therapy with first line Pembrolizumab per standard of care combined with Hemopurifier treatments . All patients will be treated with Pembrolizumab every 21 days and, during active treatment, imaging will be done after every 3rd cycle as per standard of care. As part of the first two cycles of Pembrolizumab patients will receive Hemopurifier therapy immediately prior to Pembrolizumab infusion. The Hemopurifier therapy will last 4h and patients will receive their Pembrolizumab dose as soon as logistically possible, after Hemopurifier therapy on the same day.

  Through study completion - Safety assessments will be completed at each study visits and up to two years after entry on protocol or until disease progression

• Adverse Events

  Adverse events will be graded using CTCAE v5. The proportion of patients experiencing serious adverse events at least possibly related to treatment with Hemopurifier plus Pembrolizumab will be estimated with an exact 95% binomial confidence interval. Toxicity will be assessed continuously, and the trial will be paused if any patient experiences a treatment-related Grade 3 or worse adverse event. The rule is based on a beta-binomial model with an uninformative prior (α=1, β=1), where the trial is paused if P(P(Toxicity\|Data and Prior)\>0.3)\>0.75.

  Day 1, Day 21, through study completion, up to two years

Secondary Outcomes (3)

• Levels of exosomes

  Through study completion - up to two years after entry on protocol or until disease progression

• Tumor response

  Through study completion- up to two years or until disease progression

• Survival

  Through study completion - up to two years or until disease progression

Study Arms (1)

Hemopurifier and Pembrolizumab

EXPERIMENTAL

In this clinical trial, the exosome-depleting device, the Hemopurifier, will be combined with standard of care therapy, Pembrolizumab. The purpose of the combination is to more effectively reduce immune suppression and provide a combined benefit of immune restoration for patients with recurrent/metastatic HNSCC. Therapy with the Hemopurifier will be initiated on the same day as and prior to Pembrolizumab infusion. The Hemopurifier treatment will be 4h. The subject treated with the Hemopurifier will remain in the Hemopurifier treatment area for the duration of the treatment. Pembrolizumab infusion will take place shortly after Hemopurifier treatment and may take place through the next day if needed.

Device: Hemopurifier; Drug: Pembrolizumab 200mg IV

Interventions

Hemopurifier DEVICE

Two Hemopurifier treatments on Day 1 and Day 21

Hemopurifier and Pembrolizumab

Pembrolizumab 200mg IV DRUG

Pembrolizumab 200mg IV will be administered every 21 days. One cycle is 21 days. All patients will be treated with Pembrolizumab for up to 34 cycles

Hemopurifier and Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Recurrent or metastatic HNSCC (oral cavity, oropharynx, larynx, hypopharynx) and not amenable to local therapy with curative intent (surgery or radiation therapy)
• Qualifies for Pembrolizumab monotherapy as part of standard of care (has PD-L1 CPS ≥1)
• ECOG performance status of 0-1
• Measurable disease by RECIST 1.1
• Be \> 18 years of age on day of signing informed consent
• Be willing and able to provide written informed consent for the trial
• Life expectancy of at least 12 weeks based on investigator estimate
• Adequate organ function as defined as:
• WBC ≥ 2000/μL
• Neutrophils ≥ 1500/μL
• Platelets ≥ 100 x103/μL
• Hemoglobin ≥ 8.0 g/dL
• serum creatinine \< 1.5 x ULN or creatinine clearance (CrCl) \> 40 mL/min (using the Cockcroft-Gault formula)
• AST/ALT \< 3 x ULN
• Total bilirubin \< 1.5 x ULN (except subjects with Gilbert Syndrome who can have total bilirubin \< 3mg/dL.

You may not qualify if:

• Patients with salivary gland SCC or cutaneous SCC will be excluded
• Has received systemic therapy (chemotherapy, immunotherapy, investigational therapy) for the treatment of recurrent/metastatic disease. Systemic therapy given concurrent with radiation treatment in the recurrent setting does not exclude the patient.
• Untreated brain metastasis or leptomeningeal metastasis.
• Tumor invades into the internal carotid artery or other major blood vessels whereby the treating investigator feels anti-coagulation is contraindicated.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (Prednisone \> 10mg or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
• Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) in the recurrent/metastatic setting. Patients that received any of these agents in the upfront curative intent setting can be enrolled as long as it has been 1 year since the last dose.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B or active Hepatitis C
• Has received a live vaccine within 30 days prior to the first dose of trial treatment.
• Concurrent therapy with an angiotensin-converting enzyme (ACE) inhibitor. ACE inhibitors must be discontinued at least 14 days prior to initiation of each Hemopurifier treatment and remain discontinued for 24 hours post treatment.

Sponsors & Collaborators

• Aethlon Medical Inc.: lead

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Study Officials

• Dan Zandberg, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

• Steven P. LaRosa, M.D.

  Aethlon Medical Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This trial will evaluate the use of the Hemopurifier in combination with pembrolizumab (Keytruda) in patients with advanced and/or metastatic head and neck cancer. The Hemopurifier is a blood filtration device similar to a kidney dialysis cartridge which is designed to remove small particles called exosomes from the blood. Exosomes are believed to be involved in suppression of the immune system in cancer patients. The study will evaluate whether pretreatment with the Hemopurifier before administration of pembrolizumab is safe and well tolerated and results in lower numbers of exosomes in the blood.

Study Record Dates

• First Submitted: June 20, 2020
• First Posted: July 1, 2020
• Study Start: October 22, 2020
• Primary Completion: November 14, 2022
• Study Completion: November 14, 2022
• Last Updated: December 20, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)