Clinical trial NCT02452554: Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pleuropulmonary Blastoma
Recurrent Malignant Peripheral Nerve Sheath Tumor
Recurrent Neuroblastoma
Recurrent Rhabdomyosarcoma
Recurrent Synovial Sarcoma
Wilms Tumor
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-05-22
Enrollment: 62
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

EXPLORATORY 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 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

Primary outcomes:
measure: Objective Response by Response Evaluation Criteria in Solid Tumors Version 1.1
timeFrame: Up to 18 weeks (6 courses)
measure: Incidence of Toxicities of Lorvotuzumab Mertansine, Using the NCI Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: Up to 12 months (17 courses)
Secondary outcomes:
Other outcomes:
measure: Pharmacokinetic (PK) Parameters of Lorvotuzumab Mertansine
timeFrame: 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
measure: CD56 Expression
timeFrame: Day 1 and 8 of course 1 prior to lorvotuzumab mertansine
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Downey
country: United States
facility: Kaiser Permanente Downey Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mission Bay
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Golisano Children's Hospital of Southwest Florida
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Boise
country: United States
facility: Saint Luke's Mountain States Tumor Institute
state: Idaho
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Peoria
country: United States
facility: Saint Jude Midwest Affiliate
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Care Center
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Scarborough
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Ascension Saint John Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital at Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Columbia
country: United States
facility: Prisma Health Richland Hospital
state: South Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Burlington
country: United States
facility: University of Vermont and State Agricultural College
state: Vermont
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Children's Oncology Group
name: James I Geller
role: PRINCIPAL_INVESTIGATOR
References: