Study of Sutent®/Sunitinib (SU11248) in Subjects With NF-1 Plexiform Neurofibromas

NCT01402817 | Terminated Phase 2 Results DMC

• 1 other identifier: 1104-07
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study to determine if adults and children with neurofibromatosis type 1 who have plexiform tumors given Sutent® respond to this drug therapy.

Conditions

Neurofibromatosis; NF1; Plexiform Neurofibromas

Keywords

NF1; plexiform neurofibromas; Sunitinib; Sutent®

Outcome Measures

Primary Outcomes (1)

• Disease Response

  To estimate the disease control rate (SD, PR, CR) with Sutent® in patients with neurofibromas (NF1). Tumor response criteria are determined by changes in size using all 3 dimensional measurements: width (W), transvers (T) , and length (L) measurements. Partial Response: ≥20% decrease in the sum of the products of the three perpendicular diameters of all target lesions (up to 5), taking as reference the initial baseline measurements.Stable Disease (SD): Neither sufficient decrease in the sum of the products of the three perpendicular diameters of all target lesions to qualify for PR (taking as reference the initial baseline measurements), nor sufficient increase in a single target lesions to qualify for PD, (taking as reference the smallest disease measurement since the treatment started).Progressive Disease (PD): 40% or more increase in the product of perpendicular diameters of ANY target lesion, taking as reference the smallest product observed.

  6 months

Secondary Outcomes (1)

• Volumetric Disease Evaluation

  6 months

Study Arms (1)

Sutent®/Sunitinib

EXPERIMENTAL

Upon enrollment, subjects will receive Sutent® orally. Adults (Age \>18) will receive 25mg. Children will receive 10mg/m2/day. All subjects will take the daily dose for 28 days followed by a 14 day rest period. If subjects tolerate the initial dose, adults will be increased to 37.5mg and children will be increased to 15mg/m2/day. Again, subjects will take that dose for 28 days followed by a rest period of 14 days. Adults who tolerate the increase will go up to the maximum dose of 50mg. The maximum dose for children is 15mg/m2/day.

Drug: Sutent®/Sunitinib

Interventions

Sutent®/Sunitinib DRUG

Upon enrollment, subjects will receive Sutent® orally. Adults (Age \>18) will receive 25mg. Children will receive 10mg/m2/day. All subjects will take the daily dose for 28 days followed by a 14 day rest period. If subjects tolerate the initial dose, adults will be increased to 37.5mg and children will be increased to 15mg/m2/day. Again, subjects will take that dose for 28 days followed by a rest period of 14 days. Adults who tolerate the increase will go up to the maximum dose of 50mg. The maximum dose for children is 15mg/m2/day.

Sutent®/Sunitinib

Eligibility Criteria

• Age: 3 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: patients must be ≥3 years of age and ≤65 years of age at the time of study entry
• Diagnosis: Patients must meet clinical diagnostic criteria of neurofibromatosis type 1 (NF1). Patients must have clinically significant plexiform neurofibromas (biopsy proven if possible with tissue blocks available). Clinically significant tumors are those which are potentially life threatening or are impinging on vital structures or significantly impair the quality of life from pain or other symptoms.
• Disease status: Patients must have measurable disease.
• Performance Level: Karnofsky ≥50 for patients \>10 years of age and Lansky ≥50 for patients ≤10 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.
• Prior therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study.
• Hematopoietic growth factors: At least 14 days since completion of therapy with a growth factor.
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, the period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the principal investigator.
• XRT: ≥2 weeks for local palliative XRT (small port); ≥6 months must have elapsed if ≥50% radiation of pelvis; ≥6 weeks must have elapsed if other substantial BM radiation.
• Organ function requirements
• a. Adequate bone marrow function defined as i. Peripheral absolute neutrophil count (ANC) ≥1000/µL ii. Platelet count ≥100,000/ µL(transfusion independent, iii. Hemoglobin ≥8.0 gm/dL(may receive RBC transfusions) b. Adequate renal function defined as i. Creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2 or ii. A serum creatinine based on age/gender as follows (Maximum Serum Creatinine (mg/dL)): Males: 6 to \<10 years:1; 10 to \<13 years: 1.2; 13 to \<16 years: 1.5; \>16 years 1.7. Females: 6 to \<10 years:1; 10 to \<13 years 1.2; 13 to \<16 years: 1.4; \>16 years: 1.4.
• The threshold creatinine values above were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
• c. Adequate Liver Function Defined As: i. Total bilirubin (sum of conjugated+unconjugated)≤1.5 times upper limit of normal (ULN) for age, and ii. SGPT(ALT)\<2.5 upper limit of normal ULN). For the purpose of this study, the ULN for SGPT is 45 U/L iii. Serum albumin ≥2 g/dL d. Adequate cardiac function defined as: i. Shortening fraction or ejection fraction greater than the LLN (institutional norm), and ii. Corrected QT interval ≤450 msec e. Normal Pancreatic function defined as: i. Serum amylase ≤1.5xULN and ii. Serum lipase ≤1.5xULN. f. Blood pressure within the upper limit of normal defined as: i. A blood pressure (BP) ≤ 95th percentile for age, height, and gender and not receiving medication for treatment of hypertension.
• Informed Consent: All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

You may not qualify if:

• Prior anthracycline treatment. Patients previously treated with anthracyclines (any dose) are not eligible.
• Prior Cardiac Radiation Patients previously treated with a radiation field that included the heart are not eligible.
• Pregnancy or Breast-Feeding Animal studies indicate an increased risk of death of pregnant female rats and rabbits exposed to Sutent®. Cleft lip and palate were observed in some fetuses exposed in utero to sunitinib. There is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are poet-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Concomitant Medications
• Growth factors(s): Growth factors that support platelet or white cell number or function must not have been administered within the past 14 days
• Investigational Drugs: Patients who are currently receiving another investigational drug.
• Anti-cancer agents: Patients who are currently receiving other anti-cancer agents.
• The following CYP3A4 inducers are prohibited 12 days before the start of Sutent® and during the study with Sutent®: rifampin, rifabutin, carbamazepine, Phenobarbital, phenytoin, St. John's wort, efavirenz, and tipranavir.
• Anti-thrombotic and anti-platelet agents: warfarin (Coumadin), heparin, low molecular weight heparin, aspirin, and/or ibuprofen, or other NSAIDs.
• The following CYP3A4 inhibitors are prohibited 7 days before the start of sunitinib and during the study with sunitinib: azole antifungals (itraconazole, ketoconazole); clarithromycin, erythromycin, diltiazem, verapamil, HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); delavirdine.
• Infection: Patients who have an uncontrolled infection.
• Pleural-based tumors: Pediatric patients treated on a phase II trial with imatinib had a higher than expected rate of hemorrhagic pleural effusions. Sutent® inhibits two of the same receptor tyrosine kinases as imatinib, PDGFR and c-KIT. Patients with tumors involving or abutting the pleural surface will be excluded from study. Patients with pulmonary lesions should be monitored closely for the development of hemorrhagic pleural effusions.
• Patient size: Due to dosing limitations, patients with body surface area \<0.5 m2 will be excluded from study.
• Patients with a pre-existing thyroid abnormality (hyper-or hypothyroidism) with unstable thyroid function will be excluded from study. For the purposes of this study, unstable thyroid function will be defined as thyroid function abnormalities requiring more than on e change in thyroid medication in the 6 months prior to study entry.
• Patients with history of allergic reaction attributed to Sutent® or component of Sutent® capsules.

Sponsors & Collaborators

• Indiana University: lead
• United States Department of Defense: collaborator
• Pfizer: collaborator

Study Sites (1)

Riley Hospital for Children at IU Health

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Neurofibromatoses; Neurofibroma, Plexiform

Condition Hierarchy (Ancestors)

Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Peripheral Nervous System Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Chie-Schin Shih, MD
• Organization: Indiana University School of Medicine - Pediatrics

shih2@iu.edu

317-948-8568

Study Officials

• Chie-Schin Shih, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 25, 2011
• First Posted: July 26, 2011
• Study Start: March 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: February 14, 2018
• Last Updated: March 14, 2018
• Results First Posted: May 4, 2016

Record last verified: 2018-02

Locations

US (1)