Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Areva Med LLC
Sponsor:
Information provided by (Responsible Party):
Areva Med LLC
ClinicalTrials.gov Identifier:
NCT01384253
First received: June 27, 2011
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Breast Neoplasms
Peritoneal Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms
Other: ²¹²Pb-TCMC-Trastuzumab
Biological: trastuzumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Intraperitoneal ²¹²Pb-TCMC-Trastuzumab for HER-2 Expressing Malignancy

Resource links provided by NLM:


Further study details as provided by Areva Med LLC:

Primary Outcome Measures:
  • Safety and tolerability: To measure the number of participants who experience adverse events after intraperitoneal (IP) administration of ²¹²Pb-TCMC-Trastuzumab. [ Time Frame: Assessed periodically during study treatment follow-up, up to five years. ] [ Designated as safety issue: Yes ]

    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


Secondary Outcome Measures:
  • Immunogenicity: To characterize the human immune response against ²¹²Pb-TCMC-Trastuzumab given via IP infusion. [ Time Frame: Assessed at six weeks visit ] [ Designated as safety issue: No ]
  • Anti-tumor effects: To monitor for anti-tumor effects as assessed by physical examination, radiographic imaging, and tumor marker studies. [ Time Frame: Assessed after six and twelve weeks, and then at twelve-week intervals until progression. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: To determine the plasma pharmacokinetics and assess the extent of exit of radioactivity from the peritoneal cavity by γ-camera imaging. [ Time Frame: Up to 3 days post-injection ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: July 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 of ²¹²Pb-TCMC-Trastuzumab. Serial sampling of blood, urine, and dosimetry will be performed following treatment to determine the toxicity, pharmacokinetics, immunogenicity, and antitumor effects.
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 patients will be treated at the maximum tolerated dose.
Biological: trastuzumab
4 mg/kg.
Other Name: Herceptin

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. At least 19 years of age.
  2. Life expectancy is greater than three months.
  3. Female subjects of child-bearing potential must have negative serum pregnancy test.
  4. If not surgically sterile, male and female patients of child-bearing potential must use double barrier contraception (e.g., hormonal; intrauterine device; barrier).
  5. Patients with HER-2 expressing tumors (e.g., ovarian, pancreatic, colon, gastric, endometrial, or breast) with measurable or non-measurable disease for which no standard therapy is available.
  6. HER-2 amplification by fluorescent in situ hybridization or HER-2 score of at least at least 1+ by Immunohistochemistry in more than 10% of the cells. Alternatively, HER-2 serum levels greater than 15ng/mL by ELISA.
  7. Disease must be predominantly intra-abdominal and should include documented peritoneal studding or positive peritoneal washings.
  8. Able and willing to sign an informed consent form.

Exclusion Criteria:

  1. ECOG performance status greater than 3.
  2. Any serious active disease or co-morbid condition that, in the opinion of the investigator, may interfere with the safety or the compliance with the study.
  3. Poor bone marrow reserve as defined by absolute neutrophil count less than 1.5 x 10³/cmm or platelets less than 100 x 10³/cmm within two weeks prior to initiation of treatment.
  4. Liver only metastases.
  5. Poor organ function as defined by one of the following:

    • 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01384253

Locations
United States, Alabama
University Of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Patty W. Bunch, RN, BSN, OCN    205-934-6172    pbunch@uabmc.edu   
Contact: Ronda R. Carlisle, RN, BSN, OCN    205-975-2511    rcarlisle@uab.edu   
Principal Investigator: Ruby F. Meredith, M.D., Ph.D.         
Sub-Investigator: Sharon A. Spencer, M.D.         
Sub-Investigator: Ronald D. Alvarez, M.D.         
Sub-Investigator: Charles N. Landen, M.D., M.S.         
Sub-Investigator: Andres Forero-Torres, M.D.         
Sub-Investigator: John B. Fiveash, M.D.         
United States, California
UCSD Moores Cancer Center Not yet recruiting
San Diego, California, United States
Contact: Shakeela Dad    858-822-5376    sdad@ucsd.edu   
Principal Investigator: Andrew Lowy, MD         
Sponsors and Collaborators
Areva Med LLC
Investigators
Principal Investigator: Ruby F Meredith, M.D., Ph.D. University of Alabama at Birmingham
  More Information

Additional Information:
Publications:
Responsible Party: Areva Med LLC
ClinicalTrials.gov Identifier: NCT01384253     History of Changes
Other Study ID Numbers: AREVAMED01
Study First Received: June 27, 2011
Last Updated: March 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Areva Med LLC:
HER2+
HER-2 positive
intraperitoneal
intra-abdominal
Lead 212
Radio Immunotherapy
Alpha particle
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
RIT

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Peritoneal Neoplasms
Stomach Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Breast Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms by Site
Ovarian Diseases
Pancreatic Diseases
Peritoneal Diseases
Skin Diseases
Stomach Diseases
Urogenital Neoplasms
Trastuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014