Trial record 2 of 3 for:    LUNG IMGN901

Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Children's Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT02452554
First received: May 20, 2015
Last updated: March 2, 2016
Last verified: March 2016
  Purpose
This phase II trial studies how well lorvotuzumab mertansine works in treating younger patients with Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST), or synovial sarcoma that has returned or that does not respond to treatment. Antibody-drug conjugates, such as lorvotuzumab mertansine, are created by attaching an antibody (protein used by the body's immune system to fight foreign or diseased cells) to an anti-cancer drug. The antibody is used to recognize tumor cells so the anti-cancer drug can kill them.

Condition Intervention Phase
Pleuropulmonary Blastoma
Recurrent Malignant Peripheral Nerve Sheath Tumor
Recurrent Neuroblastoma
Recurrent Rhabdomyosarcoma
Recurrent Synovial Sarcoma
Wilms Tumor
Other: Laboratory Biomarker Analysis
Biological: Lorvotuzumab Mertansine
Other: Pharmacological Study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of IMGN901 (Lorvotuzumab Mertansine; NSC: 783609) in Children With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor (MPNST) and Synovial Sarcoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Incidence of toxicities of lorvotuzumab mertansine, using the NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 months (17 courses) ] [ Designated as safety issue: Yes ]
    Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.

  • Objective response by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 18 weeks (6 courses) ] [ Designated as safety issue: No ]
    The best response of disease will be examined separately in each stratum. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.


Other Outcome Measures:
  • CD56 expression [ Time Frame: Day 1 and 8 of course 1 prior to lorvotuzumab mertansine ] [ Designated as safety issue: No ]
    The association between CD56+ expression and response will be evaluated using the exact conditional test of proportions (Fisher's Exact test). Analyses will be descriptive and exploratory and hypotheses generating in nature.

  • Pharmacokinetic (PK) parameters of lorvotuzumab mertansine [ Time Frame: Pre-treatment, end of infusion, and 2, 6, 24, 48, and 96 hours after end of infusion on day 1 of course 1, and pre-treatment, end of infusion, and 2 and 6 hours after end of infusion on day 8 of course 1 ] [ Designated as safety issue: No ]
    A descriptive analysis of PK parameters of lorvotuzumab mertansine 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). Analyses will be descriptive and exploratory and hypotheses generating in nature.


Estimated Enrollment: 150
Study Start Date: October 2015
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (lorvotuzumab mertansine)
Patients receive lorvotuzumab mertansine IV over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Lorvotuzumab Mertansine
Given IV
Other Names:
  • Anti-Human NCAM-1 Monoclonal Antibody N901
  • BB-10901
  • huN901-DM1
  • IMGN901
Other: Pharmacological Study
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the efficacy of IMGN901 (lorvotuzumab mertansine) in Wilms tumor, rhabdomyosarcoma, neuroblastoma and other cluster of differentiation (CD)56-expressing tumors such as pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST) and synovial sarcoma.

II. To determine the tolerability of the adult recommended phase 2 dose (RP2D) of IMGN901 administered as an intravenous infusion, administered on days 1 and 8 of a 21-day cycle, to children with refractory Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, MPNST, or synovial sarcoma.

III. To define and describe the toxicities of IMGN901 administered on this schedule.

SECONDARY OBJECTIVES:

I. To correlate tumor response with tumor CD56+ expression. II. To characterize the pharmacokinetics of IMGN901 in children with refractory cancer, including an assessment of impact on circulating CD56+ peripheral blood cells.

OUTLINE:

Patients receive lorvotuzumab mertansine intravenously (IV) over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

  Eligibility

Ages Eligible for Study:   12 Months to 30 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse

    • Primary strata

      • Wilms tumor
      • Rhabdomyosarcoma
      • Neuroblastoma
    • Secondary strata: miscellaneous CD56-expressing tumors:

      • Pleuropulmonary blastoma
      • Malignant peripheral nerve sheath tumor (MPNST)
      • Synovial sarcoma
  • Patients must have radiographically measurable disease (with the exception of those with neuroblastoma)

    • Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
    • Note: the following do not qualify as measurable disease:

      • Malignant fluid collections (e.g., ascites, pleural effusions)
      • Bone marrow infiltration except that detected by metaiodobenzylguanidine (MIBG) scan for neuroblastoma
      • Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted in patients with neuroblastoma who do not have measurable disease but have MIBG-avid evaluable disease
      • Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
      • Previously radiated lesions that have not demonstrated clear progression post radiation
      • Leptomeningeal lesions that do not meet the measurements noted above
  • Patients with neuroblastoma who do not have measurable disease but have MIBG-avid evaluable disease are eligible
  • Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; 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 chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • Patients must have received standard treatment appropriate for their tumor type

    • Myelosuppressive chemotherapy: patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
    • Hematopoietic growth factors: at least 14 days must have elapsed after receiving pegfilgrastim and least 7 days must have elapsed since the completion of therapy with a non-pegylated growth factor
    • Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
    • Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
    • Radiotherapy: >= 2 weeks must have elapsed since local palliative external beam radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
    • Stem cell transplant or rescue without TBI: no evidence of active graft vs. host disease and >= 2 months must have elapsed since transplant
  • For patients with solid tumors without bone marrow involvement: peripheral absolute neutrophil count (ANC) >= 1000/uL
  • For patients with solid tumors without bone marrow involvement: platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
  • For patients with solid tumors and known bone marrow metastatic disease: peripheral absolute neutrophil count (ANC) >= 750/uL
  • For patients with solid tumors and known bone marrow metastatic disease: platelet count >= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • Age 1 to < 2 years: maximum serum creatinine: 0.6 mg/dL in males and females
    • Age 2 to < 6 years: maximum serum creatinine: 0.8 mg/dL in males and females
    • Age 6 to < 10 years: maximum serum creatinine: 1 mg/dL in males and females
    • Age 10 to < 13 years: maximum serum creatinine: 1.2 mg/dL in males and females
    • Age 13 to < 16 years: maximum serum creatinine: 1.5 mg/dL in males and 1.4 mg/dL in females
    • Age >= 16 years: maximum serum creatinine: 1.7 mg/dL in males and 1.4 mg/dL in females
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
  • Serum albumin >= 2 g/dL
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients who are pregnant or breast-feeding are not eligible for this study; negative 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 therapy and for 4 weeks after the last dose of study therapy; breastfeeding women are excluded
  • Concomitant medications

    • Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible
    • Patients who have received previous treatment with IMGN901 are not eligible
    • Investigational drugs: patients who are currently receiving another investigational drug are not eligible
    • Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
    • Anti-graft-versus-host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
  • Patients who have a CNS toxicity > grade 2 are not eligible
  • Patients must not have known active central nervous system (CNS) metastases; patients with known central nervous system metastases are excluded unless treated surgically or with radiotherapy, and stable with no recurrent lesions for at least 6 months
  • Patients who have baseline peripheral neuropathy >= grade 2 are not eligible
  • Patients who have an uncontrolled infection are not eligible
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
  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: NCT02452554

Locations
United States, Alabama
Children's Hospital of Alabama Active, not recruiting
Birmingham, Alabama, United States, 35233
United States, California
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Ivan I. Kirov    714-509-8699    ikirov@choc.org   
Principal Investigator: Ivan I. Kirov         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Jeffrey S. Dome    202-476-5685    jdome@childrensnational.org   
Principal Investigator: Jeffrey S. Dome         
United States, Georgia
Children's Healthcare of Atlanta - Egleston Recruiting
Atlanta, Georgia, United States, 30322
Contact: William T. Cash    404-727-4455    thomas.cash@choa.org   
Principal Investigator: William T. Cash         
United States, Illinois
Lurie Children's Hospital-Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Stewart Goldman    312-227-9756    sgoldman@luriechildrens.org   
Principal Investigator: Stewart Goldman         
United States, Indiana
Riley Hospital for Children Active, not recruiting
Indianapolis, Indiana, United States, 46202
United States, Minnesota
University of Minnesota/Masonic Cancer Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Emily G. Greengard    612-626-2815    emilyg@umn.edu   
Principal Investigator: Emily G. Greengard         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Robert J. Hayashi    314-454-2780    info@siteman.wustl.edu   
Principal Investigator: Robert J. Hayashi         
United States, New York
Columbia University/Herbert Irving Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Alice Lee    212-305-5848    al2041@cumc.columbia.edu   
Principal Investigator: Alice Lee         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: James I. Geller    513-636-3549    james.geller@cchmc.org   
Principal Investigator: James I. Geller         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Elizabeth Fox    267-425-0113    foxe@email.chop.edu   
Principal Investigator: Elizabeth Fox         
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Jean M. Tersak    412-692-7693    jean.tersak@chp.edu   
Principal Investigator: Jean M. Tersak         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Rachel C. Brennan    901-521-9005    info@stjude.org   
Principal Investigator: Rachel C. Brennan         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Jodi Muscal    832-825-4039    jamuscal@txch.org   
Principal Investigator: Jodi Muscal         
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: James Geller Children's Oncology Group
  More Information

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02452554     History of Changes
Other Study ID Numbers: ADVL1522  NCI-2015-00746  ADVL1522  ADVL1522  U10CA180886 
Study First Received: May 20, 2015
Last Updated: March 2, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pulmonary Blastoma
Lung Neoplasms
Neoplasms
Sarcoma
Neuroblastoma
Rhabdomyosarcoma
Wilms Tumor
Sarcoma, Synovial
Nerve Sheath Neoplasms
Neurofibroma
Neurilemmoma
Neurofibrosarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases

ClinicalTrials.gov processed this record on July 21, 2016