To evaluate the safety and clinical utility of PEF treatment of advanced stage or metastatic cancer following progression on immunotherapy
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary safety endpoint will be the rate of device and/or procedure related
serious adverse events (SAEs) from the initial PEF treatment through 30 days.
AEs and SAEs will be summarized using a standard medical coding dictionary
(MedDRA). AEs and SAEs will be also be summarized based on Common Terminology
for Adverse Events (CTCAE) version 5.0, relatedness to the device and/or
procedure, and within discrete time periods in relation to the index procedure.
The primary clinical utility endpoint will be radiological assessment of
response of PEF-treated tumors and lymph nodes (e.g., change in longest
diameter of tumor, change in short axis of lymph node) at 90-day follow-up.
Secondary outcome
Secondary clinical endpoints include:
• Immunologic and biomarker assessments at baseline and follow-up including:
o Changes in phenotypes of lymphocytes (e.g. CD3+, CD4+, CD8+, Treg, NK,
Neutrophils MDSC, etc.) and serum levels of cytokines (e.g. IL-2, IL-6, IL-10,
IL-12, IFN-*) from blood samples
Other endpoints will include:
• Procedural success of accessing tumors and delivering PEF treatment.
• Duration of checkpoint inhibitor treatment beyond PEF treatment
• Patient progression free survival (PFS) at 90 days.
o PEF-treated tumor progression, new tumor appearance after PEF treatment,
transition from indeterminate to cancer of previously existing lesion
• Patient overall survival (OS) at 12 months.
• Time to focal re-intervention of PEF-treated tumor(s)
Background summary
Cancer is a major public health problem worldwide; more than 19 million new
cases of cancer were diagnosed in 2020, and nearly 10 million individuals died
from cancer2. Nearly 1.8 million people died of lung cancer in 2020 globally,
comprising 18% of all cancer deaths4, followed by colorectal, stomach, liver
and breast cancer.
Systemic treatment options for medically inoperable patients with advanced or
metastatic disease include genomic-appropriate molecularly targeted therapies,
immunotherapies, and conventional cytotoxic chemotherapy, either alone or in
combination. It is estimated that nearly 90% of patients with metastatic
non-oncogene-addicted non small-cell lung cancer (NSCLC) receive an
immunotherapy agent such as anti-PD-1/L1 axis inhibitor pembrolizumab,
nivolumab, atezolizumab, avelumab, or durvalumab, or anti-CTLA-4 inhibitor
ipilimumab with or without histologically-specific platinum chemotherapy or
targeted agent in the treatment of their cancer7. Anti-PD-1/L1 axis
immunotherapies also are approved for treatment of other late-stage solid tumor
malignancies including HCC and RCC after previous systemic treatment.
Immunotherapies have demonstrated higher response rates for selected metastatic
cancer patients, and survival benefits 2 to 3 times longer compared to
conventional cytotoxic chemotherapy8. A smaller percentage of patients have
durable responses lasting longer than 2 years, with some patients exhibiting no
active disease more than 5 years after initiating anti-PD-1 axis inhibitor
therapy9. Unfortunately, nearly 70% of patients on an immunotherapy regimen
will develop a resistance to immunotherapy and exhibit disease
progression7,10. Thus, there remains a significant unmet need to provide more
effective therapeutic strategies to further improve outcome in patients with
advanced and metastatic malignancies.
The delivery of pulse electric fields (PEF) represents a novel technique that
is currently being researched for several clinical indications. The delivery of
PEF treatment can induce cell death via the delivery of high frequency short
duration electrical energy which disrupts the cell membrane and the cells*
ability to maintain homeostasis. One form of PEF technology known as the
NanoKnife® Tissue Ablation System (AngioDynamics Inc.) is commercially
available for the surgical ablation of soft tissue and is used for the
treatment of various inoperable or difficult-to-reach tumors. Compared to other
ablative modalities used in the lung (i.e., radio frequency, microwave,
cryotherapy), PEF treatment can induce cell death in a non-thermal manner which
has several potential benefits including an improved safety profile and ability
to treat tumors near critical structures due to the preservation of the
surrounding architecture including vessels, lymphatics, and the extracellular
matrix.
Further, tumor cell death induced by PEF treatment may lead to enhanced
immunotherapy efficacy through stimulation of the body*s natural immune
response. As opposed to thermal ablative mechanisms, the non-thermal cell death
induced by PEF treatment releases a greater bolus of higher quality antigens11
from the tumor which are accessible to cells of the immune system12.
Additionally, limited encapsulation and scarring of the treated area allows
better access to these antigens and the remnant tumor itself for the immune
cells, potentially enhancing the body*s innate and adaptive response to the
tumor. A similar but modified PEF treatment to that described herein is also
being studied in the lung for a chronic bronchitis indication. A recently
published study reported a very good safety profile, with significant
reductions in goblet cell hyperplasia and chronic bronchitis symptoms13.
In this study, patients with advanced or metastatic NSCLC, HCC, or RCC that
have demonstrated at least six months of response to immunotherapy and have
radiologically documented or confirmed progressive disease consisting of up to
five sites of new growth, with each site of new growth being less than or equal
to 2 cm in longest diameter (lymph nodes >= 15mm shortest axis), will have PEF
energy delivered to the new site(s) of growth. The PEF treatment will be
adjunctive to their existing immunotherapy regimen. Patients may have had any
number of previous lines of therapy including radiotherapy but their most
recent therapy must include immunotherapy and it is expected that patients will
remain on their immunotherapy regimen for at least three months after PEF
treatment delivery, if clinically appropriate. This study design allows for an
evaluation of the safety of PEF treatment in this patient population and will
measure the effect of PEF treatment on local control of the treated tumor(s) to
determine whether this is a viable treatment option for advanced and metastatic
cancer patients.
.
Study objective
To evaluate the safety and clinical utility of PEF treatment of advanced stage
or metastatic cancer following progression on immunotherapy
Study design
A prospective, single-arm, non-randomized, multi-center, open-label study
Intervention
Treatment may be delivered via either an endoluminal or percutaneous approach
at the discretion of the clinical investigator utilizing two available device
configurations:
- Endoluminal: Galvanize Aliya System with commercially available TBNA Needle
(e.g., PeriView FLEX) and RF probe electrode
- Percutaneous: Galvanize Aliya System with compatible commercially available
RF needle and RF probe electrode
Study burden and risks
There are potential risks and side effects associated with the Galvanize PEF
procedure.
Risks potentially associated with participation in the study include the
following:
Endoluminal Procedures
• Sore throat (likely occurrence)
• Coughing (likely occurrence). Coughing up small amount of phlegm (mucous) is
common for 24 hours after the procedure. Coughing may continue for more than 24
hours.
• Hemoptysis (likely occurrence)
• Infection (moderately likely occurrence) including fever, pain or soreness
• Increase respiratory symptoms (moderately likely occurrence) including
shortness of breath, increased color and/or quantity of phlegm, cough, wheeze
or chest tightness
• Bronchial perforation (low occurrence)
• Lung abscess (low occurrence)
• Pneumothorax (low occurrence)
• Airway stenosis, scarring or injury (low occurrence) including wheezing,
hoarseness, shortness of breath and/or respiratory distress
• Significant pulmonary bleeding (low occurrence)
• Death (low occurrence)
Percutaneous Procedures
• Coughing (likely occurrence). Coughing up small amount of phlegm (mucous) is
common for 24 hours after the procedure. Coughing may continue for more than 24
hours.
• Chest pain, non-cardiac (likely occurrence)
• Needle insertion point pain (likely occurrence)
• Pneumothorax (likely occurrence),
• Air embolism (low occurrence)
• Bleeding requiring intervention (low occurrence)
• Infection (moderately likely occurrence) including fever, pain or soreness
• Bronchial perforation (low occurrence)
• Target organ abscess (low occurrence)
• Hemoptysis (moderately likely occurrence)
• Hematuria (moderately likely occurrence)
• Abdominal pain (moderately likely occurrence)
• Airway stenosis, scarring or injury (low occurrence) including wheezing,
hoarseness, shortness of breath and/or respiratory distress
• Transient abnormal organ function tests (moderately likely)
• Death (low occurrence)
Other Risks
• Shortness of breath (likely occurrence)
• Gastroparesis (low occurrence)
• Abnormal cardiac rhythm function (low occurrence) including arrhythmia,
atrial fibrillation, ventricular fibrillation,
• Allergic reaction (low occurrence) including abnormal breathing, difficulty
swallowing, anxiety, chest pain, severe cough, lightheadedness or dizziness,
sweating or fainting, swelling of the face, eyes or tongue
• Fistula (low occurrence)
• Reflex hypertension (low occurrence)
• Thrombosis (low occurrence)
• Risk of anesthesia (likely occurrence) include, nausea, vomiting, bruising at
injection sites, sore throat, hoarse voice, damage to teeth, aspiration,
urinary retention, myocardial infarction, respiratory failure, brain damage,
and death, post-procedure pain, drowsiness, slurred speech, tremor, fatigue,
low blood pressure, increased carbon dioxide in your blood, slowing of the
heart rate, anxiety, confusion, dizziness, shivering, bronchospasms,
respiratory depression, and changes in liver or heart function.
• Death (low occurrence)
Note: *Likely occurrence* refers to risks estimated to occur in more than more
than 10% of patients. Risks with *moderately likely occurrence* are estimated
to occur in 1 in 100 (1%), to 1 in 10 (10%) patients. Risks with *low
occurrence* are estimated to occur in less than 1 in 100 (1%) patients.
Other potential risk from study related tests and procedures include the
following:
• Blood draws: Mild pain, local irritation, bleeding or bruising (a black and
blue mark) at the puncture site. While rare, there is a possibility of
infection or a local blood clot with any procedure in which the skin is pierced
with a needle.
• CT Scan: Feeling of claustrophobia while performing the test. X-rays include
some amount of radiation which may increase the risk for cancer, although
unlikely.
o The effective radiation dose from one of these scans is about 4.5 mSv, which
is about the same as an average person receives from background radiation in
1.2 years.
Fluoroscopic imaging: Fluoroscopy carries some risks, as do other X-ray
procedures. The radiation dose varies depending on the individual procedure.
The radiation dose is expected to be low given the length of the procedures in
this study. The radiation risk is usually far less than other risks not
associated with radiation, such as anesthesia or sedation
• Biopsy: Bleeding, coughing up small amounts of blood or blood-tinged sputum,
pneumothorax, or scarring of the area where the biopsy was taken
The information gained from this study could result in improved development of
the technology as a better treatment for advanced stage or metastatic cancer
following progression on immunotherapy. It is unknown if additional clinical
benefit may be experienced by patients enrolled into the study following PEF
treatment.
While all interventional clinical studies pose some risks to study
participants, the study sponsor has undertaken every effort to ensure that
risks are minimized. Based on prior literature, pre-clinical animal studies,
and prior PEF clinical experience, Galvanize Therapeutics, Inc. expects the
Galvanize Aliya System to be safe for the use in this clinical study.
Industrial Road 1531
San Carlos CA 94070
US
Industrial Road 1531
San Carlos CA 94070
US
Listed location countries
Age
Inclusion criteria
• Patient is eligible if diagnosed and currently under physician care for one
of the following advanced stage or metastatic conditions:
o Stage IV non-small cell lung cancer
o Stage IV hepatocellular carcinoma
o Stage IV renal cell carcinoma
• Patient is currently receiving PD-1/PD-L1 axis immunotherapy as their most
recent line of therapy, either alone or in combination with standard of care
systemic therapy for their malignancy.
• Patient has exhibited at least 6 months of response to PD-1/PD-L1 axis
immunotherapy regimen (defined as complete response (CR), partial response
(PR), or stable disease (SD) in their index tumors per RECIST 1.1) prior to
progression.
• Patient has radiologically documented or confirmed progressive disease (per
RECIST 1.1) defined as a total of <= 5 new areas of growth on existing tumors
and/or new tumors.
• New tumors must be <= 2cm in longest diameter. New areas of growth on existing
tumors must be <= 2cm in longest diameter. Tumors and new areas of growth must
be deemed suitable by the investigator for complete treatment with PEF.
Pathologic lymph nodes must be >= 15mm in short axis.
• In the judgement of the investigator, the patient is able to remain on
PD-1/PD-L1 axis immunotherapy for at least 3 months after PEF treatment.
• New tumors and areas of growth on existing tumors are amenable to standard of
care biopsy in order to confirm disease progression.
• Patient must be willing to undergo biopsy of at least one tumor prior to PEF
treatment delivery unless there is documented histological confirmation of
malignancy within 4 weeks prior to PEF treatment.
• Patient refuses surgery and/or stereotactic body radiotherapy (SBRT).
• Life expectancy >= 12 weeks.
• ECOG performance status 0-1.
Exclusion criteria
• Patient has implanted lung devices or electronic devices.
• Patient is receiving bevacizumab concurrently with their PD-1/PD-L1 axis
immunotherapy.
• Patient has received any prior systemic therapy (systemic chemotherapy,
immunotherapy or investigational drug) in another study within 21 days prior to
study enrollment.
• Patient is scheduled to receive any concurrent chemotherapy, immunotherapy,
biologic or hormonal therapy for off-label cancer treatment while on this
study.
• Patient has unresolved adverse reaction to immunotherapy that requires dose
modification.
• Patient has received any radiation therapy within 6 weeks prior to study
enrollment.
• Patient for whom the investigator considers that the PEF treatment is not in
the patient's best interest.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04773275 |
| CCMO | NL77026.091.21 |