Trebananib in Treating Younger Patients With Relapsed or Refractory Solid Tumors, Including Central Nervous System Tumors

NCT01538095 | Completed Phase 1 DMC

• 6 other identifiers: NCI-2012-00252COG-ADVL1115ADVL1115PADVL1115_A05PAMDREVW01CDR0000725371UM1CA097452
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 22

Brief Summary

This phase I trial studies the side effects and best dose of trebananib in treating patients with solid tumors that has returned after a period of improvement or does not respond to treatment, including central nervous system tumors. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor.

Conditions

Central Nervous System Neoplasm; Solid Neoplasm

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events as assessed by the National Cancer Institute (NCI) CTCAE v 4.0

  A descriptive summary of all toxicities will be reported.

  Up to 30 days after completion of study treatment

• MTD at which fewer than one-third of patients experience dose limiting toxicity as assessed by NCI CTCAE version 4.0

  28 days

• Pharmacokinetic (PK) parameters of trebananib

  A descriptive analysis of PK parameters of trebananib will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  At baseline, at days 1, 8, 15, and 22 of course 1

Secondary Outcomes (2)

• Changes in vascular permeability relative to baseline as evaluated by MRI in patients with CNS tumors

  Baseline to up to 1 year

• Disease response assessed according to RECIST version 1.1

  Up to 1 year

Other Outcomes (1)

• Circulating antiangiogenic protein and Tie2 expressing monocyte levels

  Up to 1 year

Study Arms (1)

Treatment (trebananib)

EXPERIMENTAL

Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Trebananib

Interventions

Dynamic Contrast-Enhanced Magnetic Resonance Imaging PROCEDURE

Correlative studies

Also known as: DCE MRI, DCE-MRI, DYNAMIC CONTRAST ENHANCED MRI

Treatment (trebananib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (trebananib)

Pharmacological Study OTHER

Correlative studies

Treatment (trebananib)

Trebananib BIOLOGICAL

Given IV

Also known as: AMG 386, Angiopoietin 1/2-Neutralizing Peptibody AMG 386

Treatment (trebananib)

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Part 1: Patients must have had histologic verification of non-CNS solid tumor malignancy at original diagnosis or relapse
• Part 2: Patients must have had histologic verification of CNS malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
• Patients must have either measurable or evaluable disease
• 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
• Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50% for patients =\< 16 years of age; Note: neurologic deficits in patients with CNS tumors (Part 2 of the study) must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
• Myelosuppressive chemotherapy: at least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
• Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
• Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
• Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody
• Radiation therapy (XRT): at least 14 days after local palliative XRT (small port); at least 150 days must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
• Stem cell infusion without TBI: no evidence of active graft vs host disease and at least 56 days must have elapsed after transplant or stem cell infusion
• Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study participation, and for 6 months after completion of AMG 386 administration
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anticancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus, or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving therapeutic anticoagulation with heparin, low-molecular weight heparin, or Coumadin are not eligible for this trial
• Patients who are currently receiving aspirin, ibuprofen, or other non-steroidal anti-inflammatory drugs or anti-platelet agents are not eligible
• Patients who are receiving anti-hypertensive medications for control of blood pressure at the time of enrollment are not eligible for this trial
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who have had or are planning to have the following invasive procedures are not eligible:
• Major surgical procedure, laparoscopic procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment
• Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines (e.g., Hickman or Broviac) and at least 7 days prior to enrollment for subcutaneous port
• Core biopsy within 7 days prior to enrollment
• Fine-needle aspirate within 7 days prior to enrollment

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (22)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University/Herbert Irving Cancer Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Childrens Oncology Group

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children¿s Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

trebananib

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Officials

• Sarah Leary

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2012
• First Posted: February 23, 2012
• Study Start: February 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: October 3, 2016

Record last verified: 2016-09

Locations

US (21); CA (1)