A Study of Surufatinib in Combination With Gemcitabine in Pediatric, Adolescent, and Young Adult Patients With Recurrent or Refractory Solid Tumors
Condition: Solid Tumor; Lymphoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcoma
MeSH terms: Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma, Ewing
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to evaluate the safety and tolerability of surufatinib, thereby
      identifying the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of
      surufatinib administered in combination with gemcitabine in pediatric patients with recurrent
      or refractory solid tumors or lymphoma. The study will be conducted in 2 parts.
    

Detailed description: 
      The purpose of this study is to evaluate the safety and tolerability of surufatinib, thereby
      identifying the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of
      surufatinib administered in combination with gemcitabine in pediatric patients with recurrent
      or refractory solid tumors or lymphoma. The study will be conducted in 2 parts:

      Part 1 - evaluation of tolerability and safety of surufatinib administered in combination
      with gemcitabine, and confirmation of the recommended clinical dose of surufatinib in
      pediatric patients with recurrent or refractory solid tumors or lymphoma.

      Part 2 - evaluation of anti-tumor activity and confirmation of tolerability of surufatinib
      administered in combination with gemcitabine in pediatric patients with recurrent or
      refractory osteosarcoma, Ewing sarcoma, RMS, and non-RMS.

      Part 1 will enroll 2 to 6 patients per dose level cohort (up to 4 cohorts) with recurrent or
      refractory solid tumors. During cycle 1, surufatinib will be administered, orally, once daily
      (QD), as a single agent for 14 days followed by surufatinib daily in combination with
      gemcitabine intravenously on days 15 and 22 (cycle 1 duration=35 days) and days 1 and 8 of
      all subsequent cycles (cycle duration=21 days). Assessment based on dose limiting toxicity
      (DLT) criteria will be performed in the first 35-day cycle (DLT Evaluation Period). This
      study will utilize a rolling 6 design for part 1, with 3 dose escalation levels and 1 de
      escalation level, if needed.

      Part 2 of the study will use a Simon 2-stage design with a maximum of 18 patients per cohort
      (osteosarcoma, Ewing sarcoma, RMS, and non-RMS). Surufatinib will be administered orally at
      identified MTD/RP2D daily in combination with gemcitabine (1000 mg/m2 weekly × 2 doses)
      intravenously on days 1 and 8.

      In both parts 1 and 2, patients can remain on treatment until completing cycle 17, or until
      progressive disease, unacceptable toxicity, or death; whichever comes first.
    

Intervention name(s): Surufatinib in combination with Gemcitabine
Intervention type(s): Drug
Intervention description(s): Surufatinib in combination with Gemcitabine
Other intervention name(s): HMPL-012, sulfatinib in combination with Gemcitabine
Intervention MeSH terms: Gemcitabine
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: The study will be conducted in 2 parts:
Part 1 - evaluation of tolerability and safety of surufatinib administered in combination with gemcitabine, and confirmation of the recommended clinical dose of surufatinib in pediatric patients with recurrent or refractory solid tumors or lymphoma. Part 2 - evaluation of anti-tumor activity and confirmation of tolerability of surufatinib administered in combination with gemcitabine in pediatric patients with recurrent or refractory osteosarcoma, Ewing sarcoma, RMS, and NRSTS.
Masking: None (Open Label)
Primary purpose: Treatment