Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Recurrence

Neuroblastoma

Sarcoma

Wilms Tumor

Rhabdomyosarcoma

Sarcoma, Synovial

Nerve Sheath Neoplasms

Neurofibrosarcoma

Pulmonary Blastoma

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Myosarcoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Neoplasms, Connective Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neurofibromatoses

Neurofibroma

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Soft Tissue Sarcoma

Wilms' Tumor

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Pleuropulmonary Blastoma

Neuroepithelioma

Neurofibromatosis

All Drugs and Chemicals

Antineoplastic Agents

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Lorvotuzumab mertansine

Maytansine

Ado-Trastuzumab Emtansine

Trastuzumab

Adenosine

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

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.

Laboratory Biomarker Analysis

Lorvotuzumab Mertansine

Pharmacological Study

James I Geller

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.

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.

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

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

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.

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.

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 Clopper-Pearson confidence intervals will be constructed.

Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade for toxicities with Possible, Probable, or Definite attribution to the study drug. Tables will summarize incidence by cycle.

National Cancer Institute (NCI)

Children's Oncology Group

AE reporting is collected routinely using case report forms. The SAE table reflects NCI CTCAEs submitted by the institution, via expedited reporting (NCI AdEERs/CAeRs). The "AE Other" table reflects all CTCAEs collected; excludes those reported as SAEs. Patients who did not receive treatment before being take off study were not included in the AE tables; per protocol, AE data was not collected for those patients. Ineligible patients were excluded from both the AE and All-Cause Mortality tables.

ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles

Stratum 1: Wims Tumor

Stratum 2: Rhabdomyosarcoma

Stratum 3: Neuroblastoma

Stratum 4: Pleuropulmonary Blastoma

Stratum 5: Malignant Peripheral Nerve Sheath Tumor

Stratum 6: Synovial Sarcoma

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Results Reporting Coordinator

2 participants were excluded from analysis; 1 participant never received treatment and 1 participant was ineligible, also never receiving treatment.

Objective Response by Response Evaluation Criteria in Solid Tumors Version 1.1

Anemia: Grade 2

Anemia: Grade 3

Anemia: Grade 4

Anemia: Grade 5

Colonic fistula: Grade 2

Colonic fistula: Grade 3

Colonic fistula: Grade 4

Colonic fistula: Grade 5

Colonic perforation: Grade 2

Colonic perforation: Grade 3

Colonic perforation: Grade 4

Colonic perforation: Grade 5

Dental caries: Grade 2

Dental caries: Grade 3

Dental caries: Grade 4

Dental caries: Grade 5

Nausea: Grade 2

Nausea: Grade 3

Nausea: Grade 4

Nausea: Grade 5

Vomiting: Grade 2

Vomiting: Grade 3

Vomiting: Grade 4

Vomiting: Grade 5

Tooth infection: Grade 2

Tooth infection: Grade 3

Tooth infection: Grade 4

Tooth infection: Grade 5

Alanine aminotransferase increased: Grade 2

Alanine aminotransferase increased: Grade 3

Alanine aminotransferase increased: Grade 4

Alanine aminotransferase increased: Grade 5

Aspartate aminotransferase increased: Grade 2

Aspartate aminotransferase increased: Grade 3

Aspartate aminotransferase increased: Grade 4

Aspartate aminotransferase increased: Grade 5

Lymphocyte count decreased: Grade 2

Lymphocyte count decreased: Grade 3

Lymphocyte count decreased: Grade 4

Lymphocyte count decreased: Grade 5

Hyperglycemia: Grade 2

Hyperglycemia: Grade 3

Hyperglycemia: Grade 4

Hyperglycemia: Grade 5

Hyperuricemia: Grade 2

Hyperuricemia: Grade 3

Hyperuricemia: Grade 4

Hyperuricemia: Grade 5

Hypokalemia: Grade 2

Hypokalemia: Grade 3

Hypokalemia: Grade 4

Hypokalemia: Grade 5

Hypophosphatemia: Grade 2

Hypophosphatemia: Grade 3

Hypophosphatemia: Grade 4

Hypophosphatemia: Grade 5

Headache: Grade 2

Headache: Grade 3

Headache: Grade 4

Headache: Grade 5

Peripheral motor neuropathy: Grade 2

Peripheral motor neuropathy: Grade 3

Peripheral motor neuropathy: Grade 4

Peripheral motor neuropathy: Grade 5

Peripheral sensory neuropathy: Grade 2

Peripheral sensory neuropathy: Grade 3

Peripheral sensory neuropathy: Grade 4

Peripheral sensory neuropathy: Grade 5

All Reportable AEs: Grade 2

All Reportable AEs: Grade 3

All Reportable AEs: Grade 4

All Reportable AEs: Grade 5

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.

Laboratory Biomarker Analysis: Correlative studies

Lorvotuzumab Mertansine: Given IV

Pharmacological Study: Correlative studies

Treatment (Lorvotuzumab Mertansine)

203 treatment-cycles were reported for the analysis. 2 participants were excluded from analysis;1 participant never received treatment and 1 participant was ineligible, also never receiving treatment.

Incidence of Toxicities of Lorvotuzumab Mertansine, Using the NCI Common Terminology Criteria for Adverse Events Version 4.0

Pharmacokinetic (PK) Parameters of Lorvotuzumab Mertansine

CD56 Expression

Overall Study

Histiocytoma, Malignant Fibrous

Leiomyosarcoma

Histiocytoma

Undifferentiated Pleomorphic Sarcoma

Patients receive sapanisertib as in Phase I. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover to Arm I.

Pazopanib

Pazopanib Hydrochloride

Sapanisertib

William D Tap

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma	NCT02452554	Pleuropulmonary... Recurrent Malig... Recurrent Neuro... Recurrent Rhabd... Recurrent Synov... Wilms Tumor	Laboratory Biom... Lorvotuzumab Me... Pharmacological...	12 Months - 30 Years	Children's Oncology Group
Sapanisertib or Pazopanib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Sarcoma	NCT02601209	High Grade Sarc... Metastatic Leio... Metastatic Mali... Metastatic Syno... Metastatic Undi... Metastatic Unre... Myxofibrosarcom... Recurrent Leiom... Recurrent Malig... Recurrent Synov... Recurrent Undif... Stage III Uteri... Stage IIIA Uter... Stage IIIB Uter... Stage IIIC Uter... Stage IV Uterin... Stage IVA Uteri... Stage IVB Uteri... Unresectable Le...	Pazopanib Pazopanib Hydro... Sapanisertib	18 Years -	National Cancer Institute (NCI)
Alisertib in Treating Patients With Advanced or Metastatic Sarcoma	NCT01653028	Myxofibrosarcom... Recurrent Adult... Recurrent Leiom... Recurrent Lipos... Recurrent Malig... Recurrent Undif... Stage III Soft ... Stage IV Soft T...	Alisertib Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery	NCT02700230	Metastatic Mali... Neurofibromatos... Recurrent Malig...	Computed Tomogr... Laboratory Biom... Oncolytic Measl... Quality-of-Life... Single Photon E... Magnetic Resona... Ultrasound Imag... Biospecimen Col... Biopsy Questionnaire A...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for recurrent malignant peripheral nerve sheath tumor