Title COG ADVL1121) A Phase II study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib in Children and Young Adults with Relapsed/Refract. Rhabdomyosarcoma, Wilms Tumor, Hepatocellular, and Papillary Thyroid Carcinoma
Principal Investigator Martin Brecher, MD
Study Number 212812
Summary The primary objective of this study is to determine the objective response rate of sorafenib in children with refractory or relapsed rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), and papillary thyroid carcinoma (PTC). The secondary objectives are to estimate the time to progression for each stratum in comparison to historical controls, further define acute and long-term toxicities, and further characterize the pharmacokinetics and pharmacodynamics of sorafenib in children. This is a two-stage open label Phase II trial for children and young adults with refractory or recurrent rhabdomyosarcoma, Wilms tumor, HCC and PTC. Sorafenib will be administered orally approximately every 12 hours at 200 mg/m2/dose continuously for 28-day cycles. Toxicity will continue to be closely monitored. Response will be assessed using RECIST. Patients may receive up to 24 cycles of therapy in the absence of progressive disease or unacceptable toxicity.
- All clinical and lab studies to determine eligibility must be performed within 7 days prior to enrollment. Imaging studies must be performed within 14 days prior to study enrollment.
- Age: Rhabdomyosarcoma and Wilms Strata: patients must be > or equal to 24 months and < or equal to 30 yrs. HCC: patients must be > or equal to 24 months and < 18 yrs. PTC: patients must be > or equal to 24 months and < or equal to 21 yrs.
- Patients must have had histologic verification of Rhabdomyosarcoma, Wilms tumor, Hepatocellular Carcinoma or papillary thyroid carcinoma at original diagnosis or relapse.
- Patients must have RELAPSED or REFRACTORY disease and have radiographically MEASURABLE disease.
- Patients must have a Lansky or Karnofsky performance status score of > or equal to 50.
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study entry.
- All patients must have adequate bone marrow, renal, liver, and pulmonary function, normal serum lipase and amylase, PT, PTT, INR and adequate blood pressure control (see definitions in section 3.2.7 on pages 21-22 in protocol).
- 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 effective contraceptive methods.
- Concomitant medications (see section 3.3.2 pg. 23).
- Patients who have clinical symptoms of hepatic encephalophthy or ascites, who have an uncontrolled infection, who have received prior treatment with sorafenib, with evidence of bleeding diathesis, with known metastasis to the brain, with known Gilbert syndrome, must not be on therapeutic anti-coagulation, and those that may not be able to comply with the safety monitoring requirements are NOT ELIGIBLE for this study.