Status:
WITHDRAWN
Phase I Evaluation of Immunotoxin LMB-100 Administered by Normothermic, Intrapleural Perfusion Following Cytoreductive Surgery in Participants With Pleural Mesotheliomas, or Pleural Effusions From Cancers Expressing Mesothelin
Lead Sponsor:
National Cancer Institute (NCI)
Conditions:
Malignant Pleural Mesotheliomas (Mpm)
Malignant Pleural Effusions (Mpe)
Eligibility:
All Genders
18-120 years
Phase:
PHASE1
Brief Summary
Background: Cancers that spread into the thin tissue lining your lungs (pleura) cause serious illness. They often recur when removed. These tumors include malignant pleural mesothelioma (MPM), caused...
Detailed Description
Background * Malignant pleural mesotheliomas (MPM) are aggressive cancers with a high predilection for intrapleural recurrences despite potentially curative resections. * Pleural metastases and assoc...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- Histologically confirmed by the Laboratory of Pathology (LP), CCR, NCI mesothelinpositive malignancy arising from or metastatic to the pleura that is potentially amenable to cytoreductive surgery (R0-R2) and subsequent intrapleural perfusion based on standard of care (SOC) imaging.
- Participants with biphasic MPM must have a \< 50% sarcomatoid component.
- Participants with MPE from extra-thoracic disease may be eligible provided these sites are controlled and are less threatening than the pleural involvement LENT score \>=2 .
- Participants with stage IV cancers affecting the pleura with MPE must have received firstline standard of care systemic treatment for their malignancies.
- MPM participants must not have received any local or systemic therapy for their disease.
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade \<= 1 except hemoglobin (Hgb) \<= Grade 2, alopecia (any grade), and \<= Grade 2 peripheral neuropathy.
- Age \>18 years.
- ECOG performance status of \< 2.
- Participants must have adequate pulmonary reserve evidenced by post-operative predicted FEV1 and adjusted DLCO \>= 40% predicted.
- Room air oxygen saturation \>= 90%; otherwise pCO2 \<= 45 and pO2 \>= 60 on room air arterial blood gas (ABG).
- Adequate organ and marrow function as defined below:
- leukocytes \>= 3,000/mcL
- absolute neutrophil count \>= 1,500/mcL (without transfusion or cytokine support)
- absolute lymphocyte count \> 800/mcL
- platelets \>= 100,000/mcL
- Hgb \>= 9 g/ dL (with transfusion if necessary, within 1 week prior to treatment)
- serum albumin \>= 2.0 mg/dL
- AST/ALT \<= 2.5 X institutional ULN
- creatinine clearance (eGFR) \>= 50 mL/min/1.73 m\^2 by Cockcroft-Gault formula
- INR \<= 1.5 x ULN
- TSH, T3 and T4 within normal limits (WNL) per institutional criteria
- random serum cortisol within normal limits (WNL) per institutional criteria
- total bilirubin \< 1.5 X institutional ULN (excluding Gilbert s Syndrome)
- No active brain metastases. Participants with a history of brain metastases except those with meningeal carcinomatosis or leptomeningeal disease may be eligible for treatment a minimum of 1 week following completion of gamma knife or whole-brain radiotherapy, or 4 weeks
- following surgical resection of brain metastases provided post-treatment MRI scan reveals no evidence of active disease and no ongoing need for systemic steroids.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at the study entry, for the duration of study treatment and up to 4 months (women) or 2 months (men) after the last dose of the study drug.
- Breastfeeding participants must be willing to discontinue breastfeeding from study enrollment through two months after the LMB-100 perfusion.
- HBV-infected participants must be on antivirals and have HBV DNA \<100 IU/mL. HCV-infected participants can be enrolled if HCV RNA level is undetectable.
- The ability of the participant to understand and the willingness to sign a written informed consent.
- Participants must be enrolled into protocol 06C0014 "Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies".
- Participants must provide acceptable archival tumor samples or have at least 1 focus of disease that is amenable to tumor biopsy if necessary for confirmation of histology, and assessment of mesothelin expression.
- EXCLUSION CRITERIA:
- Active smokers.
- Participants receiving systemic steroids other than physiologic replacement doses or inhaled corticosteroids (\<= 20 mg of dexamethasone a day \[or equivalent\]) for \<= 7 consecutive days prior to treatment initiation).
- Treatment with chemotherapy, targeted therapy, immunotherapy, radiation, or surgery to an index lesion within three weeks prior to commencing protocol therapy, excluding minor surgical procedures (i.e. VATS/thoracentesis/PleurX catheter placement to palliate
- MPE).
- Treatment with another investigational agent within four weeks prior to commencing protocol therapy.
- History of allergic reactions attributed to compounds of chemical or biologic composition similar to LMB-100 or SS1P including pseudomonas endotoxin.
- Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (within 6 months prior to treatment initiation) or myocardial infarction (within 6 months prior to treatment initiation) unless revascularized, unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II), serious cardiac arrhythmia, abnormal ejection fraction (echocardiogram \[ECHO\]) \<= 40%, clinically significant bleeding or clinically significant pulmonary embolism.
- History of pneumonitis (idiopathic or drug-induced) unless cleared by pulmonary consultants.
- Receipt of any organ transplantation, including allogeneic stem-cell transplantation, except transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
- HIV-infected participants. Participants on stable doses of antiretroviral therapy whose HIV RNA is below level of quantification are eligible.
- Active COVID-19 infection.
- Active infections requiring systemic therapy.
- An additional malignancy that is progressing or requires active treatment.
- Pregnancy
- Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
Exclusion
Key Trial Info
Start Date :
January 31 2024
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 31 2024
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT05375825
Start Date
January 31 2024
End Date
January 31 2024
Last Update
February 2 2024
Active Locations (1)
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1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892