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 not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2015 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT02452554
First received: May 20, 2015
Last updated: NA
Last verified: May 2015
History: No changes posted
  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 II Study of IMGN901 (Lorvotuzumab Mertansine; IND #: TBD, 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: May 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 hour 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
  • LORVOTUZUMAB MERTANSINE
Other: Pharmacological Study
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the efficacy of IMGN901 (lorvotuzumab mertansine) in Wilms tumor, rhabdomyosarcoma and neuroblastoma and other cluster of differentiation (CD)56-expresing 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 hour 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:   13 Months to 30 Years
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-expresing 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 must not have baseline peripheral neuropathy of grade 2 or higher
  • Patients must not have known central nervous system (CNS) metastases
  • Central nervous system function defined as:

    • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
    • CNS toxicity =< grade 2
  • 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; 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 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, Pennsylvania
Children's Oncology Group Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: James I. Geller, MD    513-636-6312    James.Geller@cchmc.org   
Principal Investigator: James I. Geller, MD         
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: James Geller, MD Children's Oncology Group
  More Information

No publications provided

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: May 20, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pulmonary Blastoma
Lung Neoplasms
Neoplasms
Nerve Sheath Neoplasms
Neurilemmoma
Neuroblastoma
Neurofibroma
Neurofibrosarcoma
Rhabdomyosarcoma
Sarcoma
Sarcoma, Synovial
Wilms Tumor
Fibrosarcoma
Genetic Diseases, Inborn
Kidney Diseases
Kidney Neoplasms
Myosarcoma
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Fibrous Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Muscle Tissue
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplastic Syndromes, Hereditary
Nervous System Diseases

ClinicalTrials.gov processed this record on September 01, 2015