Direct Injection of Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma
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|ClinicalTrials.gov Identifier: NCT04345705|
Recruitment Status : Not yet recruiting
First Posted : April 14, 2020
Last Update Posted : April 14, 2020
The purpose of this study is to offer a novel cancer vaccine called poly-ICLC (Hiltonol®) for subjects with malignant pleural mesothelioma by directly injecting the vaccine into the tumor.
This trial will enroll a maximum of 18 patients with biopsy proven malignant pleural mesothelioma who are surgically resectable. Subjects will undergo core biopsies of their mesothelioma followed by direct injection of Poly ICLC, a TLR3 agonist which has been shown to have biological and immunological effects. Within two to three weeks following the injection, the patients will undergo a pleurectomy/decortication or EPP, as is standard of care. Tissue resected at that time will be compared to tissue obtained at biopsy prior to the injection of the immunological agent.
|Condition or disease||Intervention/treatment||Phase|
|Mesothelioma||Drug: Poly ICLC||Phase 1|
This is a phase I study of intratumoral Poly-ICLC, a TLR3 agonist modulating the tumor microenvironment (TME), in subjects with potentially resectable, malignant pleural mesothelioma (MPM). Patients will be eligible for the study if they have had a CT and/or PET CT imaging suggestive of MPM, pathologically confirmed MPM and are surgically operable. If the patient is deemed to be a good candidate, he or she will be consented by the surgeon or the collaborating medical oncologist. Subjects who consent will go on to receive a core needle biopsy and fine needle aspiration (FNA) by an interventional radiologist under CT guidance. FNA and up to four core biopsy samples will be obtained from the tumor lesion. Poly-ICLC will be delivered to the interventional suite prior to the biopsy performed. Pathology will be confirmed either by surgical biopsy or interventional radiology guided biopsy prior to core biopsy retrieval. Patients will receive up to 4 intra-tumoral (IT) injections of Poly-ICLC of 0.1, 0.5, or 1.0mg (0.5ml) in a dose escalation design. The injection sites will be labeled on a diagram by the interventional radiologist to communicate the location to the thoracic surgeon.
Post injection of the Poly-ICLC, the patient will be monitored in the IR suite for any adverse events for at least two hours which is current standard of care to assess for pneumothorax. A study nurse will measure the subject's vital signs including pulse oximetry and will assess the injection site for two thirty minute intervals and again at two hours. Additional laboratory tests may be performed at the discretion of the study physician if signs and symptoms of an adverse event become apparent. A chest radiograph will also be obtained at two hours post procedure as is current standard of care post pleural biopsy. In the absence of adverse events subjects will be allowed to go home two hours after injection Post biopsy, the patient will be seen again by the thoracic surgeon who will consent the patient for surgery and institute the appropriate workup as per the standard of care. Patients will have preoperative tests that may include pulmonary function test, echocardiogram, and PET-CT but these will be left to the discretion of the treating thoracic surgeon. Up to 21 days post biopsy/Poly-ICLC injection (per the standard of care); the patient will undergo surgical resection of the lesion. Both biopsy specimen and surgically resected tissue will be stored in the department of pathology per current guidelines. In addition, tissue and blood will be procured for research purposes and processed in the Sinai Immunotherapy Core lab. The pre-IT biopsy and the surgically resected tissue, along with peripheral blood and plasma specimens, will then be compared to evaluate immunological target alterations after drug exposure with Poly-ICLC. Postoperative care and follow up will be performed per the standard of care from the treating surgeon. Radiation and chemotherapy will be given postoperatively at the discretion of the treating radiation and medical oncologists if deemed necessary.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
Phase 1: Dose Escalation Study
This protocol consists of a phase I study to determine the safety and toxicity of intratumoral (IT) Polyinosinicpolycytidylic acid stabilized with polylysine and carboxymethylcellulose (Poly-ICLC, Hiltonol®) prior to surgical resection for malignant pleural mesothelioma. It will evaluate the maximum tolerated dose (MTD) of this schedule and describe the toxicities by frequency and by grade.
The proposed doses of intratumoral (IT) Polyinosinicpolycytidylic acid are 0.1, 0.5, and 1.0 mg.
Dose-limiting toxicity (DLT) will be defined as any of the following AEs:
|Masking:||None (Open Label)|
|Official Title:||Direct Injection of Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma|
|Estimated Study Start Date :||May 2020|
|Estimated Primary Completion Date :||May 2022|
|Estimated Study Completion Date :||May 2022|
Experimental: Intratumoral Poly-ICLC
Participants with potentially resectable, malignant pleural mesothelioma (MPM)
Drug: Poly ICLC
receive up to 4 intra-tumoral (IT) injections of Poly-ICLC of 0.1, 0.5, or 1.0 mg (0.5ml) in a dose escalation design.
Other Name: Hiltonol®
- Maximum tolerated dose (MTD) [ Time Frame: 3 months ]Maximum tolerated dose (MTD) of intratumoral (IT) Polyinosinic-Polycytidylic acid-poly-L-lysine carboxymethylcellulose (Poly-ICLC, Hiltonol®) prior to surgical resection for patients with malignant pleural mesothelioma to evaluate safety and toxicity.
- Progression-free survival (PFS) [ Time Frame: 5 years ]Progression-free survival of subjects treated with intratumoral (IT) Poly-ICLC followed by surgical resection defined as the time of injection until the first date that progression is confirmed or date of death.
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): NCT04345705
|Contact: Andrea Wolf, MDemail@example.com|
|Contact: Raja Flores, MDfirstname.lastname@example.org|
|United States, New York|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|Contact: Raja Flores, MS 212-241-9466 email@example.com|
|Sub-Investigator: Andrea Wolf, MD|
|Principal Investigator:||Raja Flores, MD||Icahn School of Medicine at Mount Sinai|
|Principal Investigator:||Andrea Wolf, MD||Icahn School of Medicine at Mount Sinai|