HGS-ETR2 to Treat Children With Solid Tumors

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00428272
First received: January 25, 2007
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

Background

  • HGS-ETR2 is a monoclonal antibody, produced in the laboratory from human genes.
  • HGS-ETR2 targets a protein called the TRAIL receptor that is located on the surface of some tumor cells. When the TRAIL receptor is activated, it can cause the tumor cell to self-destruct.

Objectives:

  • To determine the highest dose of HGS-ETR2 that can be given safely in children and young adults with cancer.
  • To study the pharmacology (how the body handles the drug) of HGS-ETR2 by measuring the amount of drug in the bloodstream over time before and after a dose is given to the patient.
  • To determine if HGS-ETR2 can stop or slow tumor growth.
  • To determine whether proteins in tumor tissue before treatment can predict whether the tumor will respond to HGS-ETR2 therapy.

Eligibility:

-Patients 1 to 21 years of age with solid cancers that do not respond to standard therapy.

Design:

  • HGS-ETR2 is given through a vein (intravenously, IV) once every 14 days. Each treatment cycle is 28 days long and consists of two doses of HGS-ETR2.
  • The dose of HGS-ETR2 is increased in successive small groups of patients until the maximum tolerated dose (highest dose with acceptable side effects) is determined.
  • During the treatment period, patients have a physical examination at least once a week, and routine blood tests at least twice a week. These tests are done less frequently in later treatment cycles.
  • Additional blood samples are drawn for immunology and pharmacology studies.
  • Tests to monitor the size of the tumor (X-rays, CT scans, MRI, PET scans) are done periodically throughout the treatment period.
  • Patients may continue to receive HGS-ETR2 until unacceptable side effects develop or the tumor grows.

Condition Intervention Phase
Metastatic Tumors
Drug: HGS-ETR2
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Trial of Monoclonal Antibody HGS-ETR2 (Lexatumumab) With or Without Interferon Gamma in Patients With Refractory Pediatric Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To determine the tolerance of the adult maximum tolerated dose and dose limiting toxicities of lexatumumab in patients with refractory pediatric solid tumors.

Secondary Outcome Measures:
  • To quantify tumor response to HGS-ETR2.

Enrollment: 19
Study Start Date: December 2006
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: HGS-ETR2
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

AGE: Patients must be greater than or equal to 1 years and less than or equal to 30 years of age in order to encompass a broad range of ages in children as well as to capture the young adult population which is highly represented in many of these types of sarcomas being studied.

DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing s sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilm s tumor, Hodgkin's or non-Hodgkin's lymphoma. Patients with primary or untreated metastatic CNS tumors or primary or metastatic hepatic tumors will not be treated on this study.

MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable tumors.

PRIOR THERAPY:

The patient s cancer must have relapsed following or failed to respond to standard therapy, and the patient s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.

Patients must have completed their last dose of irradiation, chemotherapy, monoclonal antibody, or investigational therapy at least 4 weeks prior to enrollment or their last dose of nitrosurea (CCNU, BCNU) 6 weeks prior to enrollment. For patients who have undergone autologous stem cell transplantation, at least 3 months must have elapsed since transplant.

Patients must have recovered from the toxic effects of all prior therapy prior to enrollment.

Patients must have been off colony stimulating factors (e.g. G-CSF, GM-CSF, Epo) for at least 72 hours prior to enrollment.

Patients must have completed any biological therapy (including investigational therapies) at least 7 days prior to study entry.

PERFORMANCE STATUS: Patients greater than 10 years old must have a Karnofsky Score of greater than or equal to 50 and children less than or equal to 10 years old must have a Lansky score of greater than 50. Patients who are unable to walk because of paralysis or weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.

HEMATOLOGIC FUNCTION: Patients must have adequate bone marrow function, defined as a peripheral absolute granulocyte count of greater than or equal to 1000/microliter, hemoglobin greater than or equal to 8 gm/dl, and a transfusion independent platelet count greater than or equal to 75,000/microliter.

Cardiac Function: Patients must have an ejection fraction of greater than 40% via MUGA or Echo or a shortening fraction greater than 27% by Echo and must not have had a history of congestive heart failure.

HEPATIC FUNCTION: Aspartate transaminase (AST) and alanine transaminase (ALT), less than or equal to 2.5-fold the upper limit of normal (ULN). Direct bilirubin within normal limits.

RENAL FUNCTION: Patients must have normal age-adjusted serum creatinine (see Table below) OR a creatinine clearance greater than or equal to 60 mL/min/1.73 m(2).

Age Less than or equal to 5 with a max serum creatinine (mg/dl) of 0.8

Age less than 5 less than or equal to 10 with a max serum creatinine (mg/dl) of 1.0

Age less than 10 less than or equal to 15 with a max serum creatinine (mg/dl) of 1.2

Less than 15 with a max serum creatinine (mg/dl) of 1.5

INFORMED CONSENT: All patients or their legal guardians (if the patients is less than18 years old) must sign a document of informed consent (Pediatric Oncology Branch, NCI screening protocol for NIH patients) prior to performing studies to determine patient eligibility. After confirmation of eligibility, all patients or their legal guardians must voluntarily sign the IRB approved protocol specific informed

this study and their willingness to receive the therapy and to undergo the research studies involved including pharmacokinetic studies. The consent must be signed before any protocol related studies are performed (This does not include routine laboratory tests or imaging studies required to establish eligibility). When appropriate, pediatric patients will be included in all discussions in order to obtain verbal assent. Assent will be obtained according to local IRB requirements.

DURABLE POWER OF ATTORNEY (DPA): Patients who are greater than or equal to 18 years of age will be offered the opportunity to assign a DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired.

BIRTH CONTROL: Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study and for 60 days following the last dose.

EXCLUSION CRITERIA:

Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient s ability to tolerate the agents in this trial or are likely to interfere with the study procedures or results.

Patients with a history of allogeneic bone marrow transplantation. Patients who have received autologous stem cell transplantation are eligible greater than 3 months after completion of therapy if they meet other eligibility requirements.

Patients with hepatic tumors or metastases are excluded due to the potential for hepatotoxicity with agents that target the TRAIL-R pathway. Patients with primary CNS tumors will be excluded due to unknown penetration into the CNS.

Untreated CNS metastases will render the patient ineligible however patients with a previous history of CNS metastases are eligible if: the metastases have been treated with surgery and/or radiotherapy, are clinically stable as evidenced by no requirements for corticosteroids, the patient has no evolving neurologic deficits and no change in residual brain abnormalities without specific therapy over 6 weeks.

Pregnant or breastfeeding females are excluded because the risks of lexatumumab to the developing fetus or nursing child are unknown.

Patients currently receiving other investigational agents.

History of any infection requiring hospitalization or parenteral antibiotics within 2 weeks of study entry.

Co-existing medical illness that would place the subject at undue risk.

On immunosupressant therapy (with the exception of prednisone up to 10 mg/day, or dexamethasone up to 4 mg/day), or with known human immunodeficiency virus (HIV) infection or hepatitis B or C. Subjects with immune deficiency are excluded due to their increased risk of life threatening toxicity when treated with anticancer agents.

  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: NCT00428272

Locations
United States, Maryland
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Sponsors and Collaborators
Investigators
Principal Investigator: Crystal L Mackall, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00428272     History of Changes
Obsolete Identifiers: NCT01445093
Other Study ID Numbers: 070040, 07-C-0040
Study First Received: January 25, 2007
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Trail Receptor
Trail
Malignant Tumor
Metastatic Tumor
Pediatric Solid Tumor
Ewing Sarcoma
Osteosarcoma
Neuroblastoma
Rhabdomyosarcoma

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on October 20, 2014