Direct Injection of Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma

Mesothelioma Clinical Trial

Official title:

Direct Injection of Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04345705
• Other study ID #: GCO 19-2701
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 2020
• Est. completion date: May 2022

Study information

• Verified date: April 2020
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Andrea Wolf, MD
• Phone: 212-241-9502
• Email: andrea.wolf[@]mountsinai.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: May 2022
• Est. primary completion date: May 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Biopsy proven malignant pleural mesothelioma

a. If biopsied at an outside institution, must have a tissue block sample available

• Deemed to be surgically resectable by a dedicated thoracic surgeon.

• Acceptable hematologic, renal and liver function as follows:

1. Absolute neutrophil count > 1000/mm3

2. Platelets > 50,000/mm3,

3. Creatinine = 2.5 mg/dl,

4. Total bilirubin = 1.5 mg/dl,

5. Transaminases = 2 times above the upper limits of the institutional normal.

6. INR<1.6 if off of anticoagulation. Patients on anticoagulation therapy with an INR>1.6 may be enrolled at the discretion of the investigator if they have not had any episodes of severe hemorrhage and if the site to be injected is fully surrounded by pleura where achieving homeostasis would be complicated.

• Patient must be able to provide informed consent

• Subject is willing to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

• Serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive Poly-ICLC with reasonable safety.

• History of any pulmonary process that precludes a biopsy to be done safely.

• Severe pulmonary hypertension; having a history of pulmonary hypertension or an estimated PA systolic pressure of >60mmHg as measured by tricuspid regurgitation on preoperative echocardiogram.

• Subject unable to cooperate in terms of maintaining position during the procedure.

• AIDS defined as a CD4 count less than 200 in the context of HIV seropositivity or chronically is taking immunosuppressive medication such as steroids or transplant related medications.

• Persistent toxicity from recent therapy that has not sufficiently resolved in the judgment of the study physician.

• Subject has an active infection requiring therapy.

• Subject has had an allogenetic tissue/solid organ transplant.

• Subject has active autoimmune disease that has required systemic treatment within the past 2 years (eg, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

• Subject has known active Hepatitis B, Hepatitis C or tuberculosis. Active Hepatitis B is defined as a known positive HBsAg result. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV ribonucleic acid (RNA) results greater than the lower limits of detection of the assay.

• Concomitant comorbidities that are uncontrolled that would preclude the patient from being a surgical candidate including uncontrolled CHF, diabetes or heart disease

• Women with a positive serum or urine pregnancy test at baseline, or are pregnant or breastfeeding.

Related Conditions & MeSH terms

• Mesothelioma

Intervention

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.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Raja M Flores	Oncovir, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)	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.	3 months
Secondary	Progression-free survival (PFS)	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.	5 years