Kidney Cancer Clinical Trial

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

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.

View Full Description

Full 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.

View Eligibility Criteria

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

Study is for people with:

Kidney Cancer

Phase:

Phase 2

Estimated Enrollment:

62

Study ID:

NCT02452554

Recruitment Status:

Completed

Sponsor:

Children's Oncology Group

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 69 Locations for this study

See Locations Near You

Children's Hospital of Alabama
Birmingham Alabama, 35233, United States
Arkansas Children's Hospital
Little Rock Arkansas, 72202, United States
Kaiser Permanente Downey Medical Center
Downey California, 90242, United States
Loma Linda University Medical Center
Loma Linda California, 92354, United States
Children's Hospital Los Angeles
Los Angeles California, 90027, United States
Children's Hospital and Research Center at Oakland
Oakland California, 94609, United States
Children's Hospital of Orange County
Orange California, 92868, United States
University of California Davis Comprehensive Cancer Center
Sacramento California, 95817, United States
Rady Children's Hospital - San Diego
San Diego California, 92123, United States
UCSF Medical Center-Mission Bay
San Francisco California, 94158, United States
Children's Hospital Colorado
Aurora Colorado, 80045, United States
Yale University
New Haven Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington Delaware, 19803, United States
Children's National Medical Center
Washington District of Columbia, 20010, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers Florida, 33908, United States
Nicklaus Children's Hospital
Miami Florida, 33155, United States
AdventHealth Orlando
Orlando Florida, 32803, United States
Johns Hopkins All Children's Hospital
Saint Petersburg Florida, 33701, United States
Children's Healthcare of Atlanta - Egleston
Atlanta Georgia, 30322, United States
Kapiolani Medical Center for Women and Children
Honolulu Hawaii, 96826, United States
Saint Luke's Mountain States Tumor Institute
Boise Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago Illinois, 60637, United States
Saint Jude Midwest Affiliate
Peoria Illinois, 61637, United States
Riley Hospital for Children
Indianapolis Indiana, 46202, United States
Saint Vincent Hospital and Health Care Center
Indianapolis Indiana, 46260, United States
University of Kentucky/Markey Cancer Center
Lexington Kentucky, 40536, United States
Ochsner Medical Center Jefferson
New Orleans Louisiana, 70121, United States
Eastern Maine Medical Center
Bangor Maine, 04401, United States
Maine Children's Cancer Program
Scarborough Maine, 04074, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor Michigan, 48109, United States
Wayne State University/Karmanos Cancer Institute
Detroit Michigan, 48201, United States
Ascension Saint John Hospital
Detroit Michigan, 48236, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids Michigan, 49503, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis Minnesota, 55455, United States
Mayo Clinic
Rochester Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson Mississippi, 39216, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Mercy Hospital Saint Louis
Saint Louis Missouri, 63141, United States
Dartmouth Hitchcock Medical Center
Lebanon New Hampshire, 03756, United States
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
Mount Sinai Hospital
New York New York, 10029, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York New York, 10032, United States
State University of New York Upstate Medical University
Syracuse New York, 13210, United States
Sanford Broadway Medical Center
Fargo North Dakota, 58122, United States
Cincinnati Children's Hospital Medical Center
Cincinnati Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland Ohio, 44106, United States
Nationwide Children's Hospital
Columbus Ohio, 43205, United States
Oregon Health and Science University
Portland Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh Pennsylvania, 15224, United States
Prisma Health Richland Hospital
Columbia South Carolina, 29203, United States
St. Jude Children's Research Hospital
Memphis Tennessee, 38105, United States
Vanderbilt University/Ingram Cancer Center
Nashville Tennessee, 37232, United States
Dell Children's Medical Center of Central Texas
Austin Texas, 78723, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas Texas, 75390, United States
Cook Children's Medical Center
Fort Worth Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston Texas, 77030, United States
Primary Children's Hospital
Salt Lake City Utah, 84113, United States
University of Vermont and State Agricultural College
Burlington Vermont, 05405, United States
Children's Hospital of The King's Daughters
Norfolk Virginia, 23507, United States
Seattle Children's Hospital
Seattle Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane Washington, 99204, United States
West Virginia University Healthcare
Morgantown West Virginia, 26506, United States
University of Wisconsin Hospital and Clinics
Madison Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee Wisconsin, 53226, United States

How clear is this clinincal trial information?

Study is for people with:

Kidney Cancer

Phase:

Phase 2

Estimated Enrollment:

62

Study ID:

NCT02452554

Recruitment Status:

Completed

Sponsor:


Children's Oncology Group

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.

Please confirm you are a US based health care provider:

Yes, I am a health care Provider No, I am not a health care provider