Safety Study Of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy

Study Overview

Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy

Monoclonal antibodies can transport and deliver radioactive elements capable of releasing sufficient amounts of energy to destroy tumor cells. In this clinical trial, we will study alpha particle radio immunotherapy using lead-212 (²¹²Pb), an isotope with a short path length targeted to malignant cells by the trastuzumab antibody, as a potential treatment for metastatic diseases. This Phase I trial is designed to determine the toxicity profile of ²¹²Pb-TCMC-Trastuzumab, its dose-limiting toxicities, and its anti-tumor effects in patients with HER-2 positive intraperitoneal cancers.

N/A

Breast Neoplasms
Peritoneal Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms

OTHER: ²¹²Pb-TCMC-Trastuzumab
BIOLOGICAL: trastuzumab

AREVAMED01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-06-27	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2016-09-29
First Submitted that Met QC Criteria 2011-06-28	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2016-09-30
First Posted (ESTIMATED) 2011-06-29	Results First Posted N/A	Last Verified 2016-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase I: Dose escalation In preparation for the study, patients screened and eligible will have a peritoneal catheter placed and the evening prior to the injection of the labeled antibody will receive furosemide. Herceptin will be administered IV followed by a single IP infusion	OTHER: ²¹²Pb-TCMC-Trastuzumab The starting dose level will be 200 μCi/m² of ²¹²Pb-TCMC-Trastuzumab. Three to six patients will be treated at each dose level, and dose escalation will proceed if no more than 1 out of 6 patients in a cohort experiences dose limiting toxicity. Six patien BIOLOGICAL: trastuzumab 4 mg/kg.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Phase I: Dose escalation

In preparation for the study, patients screened and eligible will have a peritoneal catheter placed and the evening prior to the injection of the labeled antibody will receive furosemide. Herceptin will be administered IV followed by a single IP infusion

OTHER: ²¹²Pb-TCMC-Trastuzumab

The starting dose level will be 200 μCi/m² of ²¹²Pb-TCMC-Trastuzumab. Three to six patients will be treated at each dose level, and dose escalation will proceed if no more than 1 out of 6 patients in a cohort experiences dose limiting toxicity. Six patien

BIOLOGICAL: trastuzumab

4 mg/kg.

Primary Outcome Measures	Measure Description	Time Frame
Safety and tolerability: To measure the number of participants who experience adverse events after intraperitoneal (IP) administration of ²¹²Pb-TCMC-Trastuzumab.	Adverse events considered dose limiting toxicity: * Grade 3 elevations of ALP, bilirubin, ALT, or AST lasting ≥7 days * Grade 3 elevations of serum creatinine within 6 weeks of treatment * Grade 2 elevations of serum creatinine lasting ≥7 days that occur after 6 weeks * Grade 3 proteinuria * Any other Grade 3 or 4 non-hematologic toxicity * Grade 4 neutropenia lasting ≥7 days or febrile neutropenia of any duration * Grade 3 thrombocytopenia that fails to recover to ≤ Grade 2 at 6 weeks * Grade 4 thrombocytopenia lasting ≥7 days or thrombocytopenia accompanied by bleeding	Assessed periodically during study treatment follow-up, up to five years.

Secondary Outcome Measures	Measure Description	Time Frame
Immunogenicity: To characterize the human immune response against ²¹²Pb-TCMC-Trastuzumab given via IP infusion.		Assessed at six weeks visit
Anti-tumor effects: To monitor for anti-tumor effects as assessed by physical examination, radiographic imaging, and tumor marker studies.		Assessed after six and twelve weeks, and then at twelve-week intervals until progression.
Pharmacokinetics: To determine the plasma pharmacokinetics and assess the extent of exit of radioactivity from the peritoneal cavity by γ-camera imaging.		Up to 3 days post-injection

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
19 Years

Accepts Healthy Volunteers:

Total bilirubin greater than 1.5 upper limits of normal (ULN)
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) greater than 2.5 ULN or greater than 5 ULN in case of documented liver metastasis
Serum creatinine greater than ULN, except if calculated creatinine clearance greater than 60 mL/min
Urine Protein/Creatinine Ratio greater than 1 on morning spot urinalysis or proteinuria greater than 500 mg/24 h 6. Breast-feeding woman. 7. No resolution of all specific toxicities (excluding alopecia) related to any prior anticancer therapy to Grade 2 according to the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v.4.03 or nausea and vomiting to Grade 3 and uncontrolled with anti-emetics. 8. Wash out period of less than three weeks from previous anti-tumor therapy or any investigational treatment (and less than six weeks in case of prior nitroso-urea and or mitomycin C treatment) of scheduled date of administration. 9. Wash out period of less than one week from last palliative dose of radiotherapy. 10. Any other severe underlying medical conditions that could impair the ability to participate in the study or the interpretation of its results related to the investigational product such as:

Patients with abnormal cardiac function defined by a left ventricular ejection fraction (LVEF) less than 50% by echocardiogram (ECHO) or multi gated acquisition (MUGA) scan
Patients with previous history of acute cardiac failure 11. Clinical symptoms of bowel obstruction, evidence of rectosigmoid bowel involvement on exam, or transmural bowel wall involvement on computed tomography (CT) or magnetic resonance imaging (MRI). 12. Prior whole abdomen radiation therapy exceeding 4Gy, intraperitoneal radionuclide therapy, bone marrow transplant, or stem cell transplant. 13. History of Human Immunodeficiency Virus (HIV) antibody by enzyme-linked immunosorbent assay (ELISA) or negative by Western blot (if ELISA is positive) or hepatitis B surface antigen (HBsAg) because of the potential for added toxicity from the radiolabeled antibody among patients infected with these viruses. 14. Detectable human anti-human antibody (HAHA) if there is any history of monoclonal antibody exposure. 15. Iodine allergy if the patient is unwilling to accept radiation to the thyroid from uptake of radionuclide without blocking. 16. Allergy to furosemide if the patient is unwilling to accept radiation risk without these agents and alternative is not feasible. 17. History of cumulative anthracycline therapy exceeding 200 mg/m² for doxorubicin or comparable low dose of other anthracyclines.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Ruby F Meredith, M.D., Ph.D., University of Alabama at Birmingham

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Meredith RF, Torgue J, Azure MT, Shen S, Saddekni S, Banaga E, Carlise R, Bunch P, Yoder D, Alvarez R. Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. Cancer Biother Radiopharm. 2014 Feb;29(1):12-7. doi: 10.1089/cbr.2013.1531. Epub 2013 Nov 14.
Meredith R, Torgue J, Shen S, Fisher DR, Banaga E, Bunch P, Morgan D, Fan J, Straughn JM Jr. Dose escalation and dosimetry of first-in-human alpha radioimmunotherapy with 212Pb-TCMC-trastuzumab. J Nucl Med. 2014 Oct;55(10):1636-42. doi: 10.2967/jnumed.114.143842. Epub 2014 Aug 25.

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