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Trial record 1 of 2 for:    mesothelioma | First posted from 04/03/2020 to 04/17/2020
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Direct Injection of Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04345705
Recruitment Status : Not yet recruiting
First Posted : April 14, 2020
Last Update Posted : April 14, 2020
Oncovir, Inc.
Information provided by (Responsible Party):
Raja M Flores, Icahn School of Medicine at Mount Sinai

Brief 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.

Condition or disease Intervention/treatment Phase
Mesothelioma Drug: Poly ICLC Phase 1

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
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:

  1. grade > 2 pneumonitis
  2. grade > 3 fever
  3. grade > 3 fatigue
  4. grade > 3 lung infection
  5. grade ≥ 3 hypersensitivity reaction
  6. Any AE preventing a patient from proceeding with surgery
  7. grade ≥ 3 weakness
  8. grade ≥ 3 abdominal pain
  9. grade ≥ 3 hepatobiliary disorder
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
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®

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT04345705

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Contact: Andrea Wolf, MD 212-241-9502
Contact: Raja Flores, MD 212.241.9466

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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   
Sub-Investigator: Andrea Wolf, MD         
Sponsors and Collaborators
Raja M Flores
Oncovir, Inc.
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Principal Investigator: Raja Flores, MD Icahn School of Medicine at Mount Sinai
Principal Investigator: Andrea Wolf, MD Icahn School of Medicine at Mount Sinai
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Responsible Party: Raja M Flores, Professor and System Chair | Thoracic Surgery, Icahn School of Medicine at Mount Sinai Identifier: NCT04345705    
Other Study ID Numbers: GCO 19-2701
First Posted: April 14, 2020    Key Record Dates
Last Update Posted: April 14, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Raja M Flores, Icahn School of Medicine at Mount Sinai:
Lung Cancer
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs