recurrent or refractory solid tumors or lymphoma (not central nervous system) who have a known or expected dysfunction of vascular endothelial growth factor receptor-1, -2, and -3
Conditions
Interventions
Product Name: Surufatinib
Product Code: HMPL-012
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SURUFATINIB
CAS Number: 1308672-74-3
Current Sponsor code: HMPL-012
Concentration unit: mg mill
Sponsors
HUTCHMED Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age: At time of study enrollment, patients must be a. Part 1 (including PK expansion cohort): from birth to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnancy or breastfeeding: Pregnant or breastfeeding females will not be entered into this study due to risks of fetal and teratogenic AEs as seen in animal toxicity studies. Pregnancy tests must be obtained in females who are postmenarchal. 2. Concomitant medications a. Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible (if used to modify immune AEs related to prior therapy, =14 days must have elapsed since last dose of corticosteroid). b. Investigational drugs: patients who are currently receiving another investigational drug are not eligible. c. Anticancer agents: patients who are currently receiving other anticancer agents are not eligible. d. QTc agents: patients who are receiving drugs that prolong QTc within the last 7 days are not eligible. e. Patients may not be on clozapine, natalizumab, leflunomide, tofacitinib, or warfarin as these may interact with gemcitabine. f. Patients who are receiving medications that are strong inhibitors or inducers of CYP3A4 3. Thyroid replacement therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 3 weeks prior to study enrollment. 4. Patients who have uncontrolled infection are not eligible. 5. Patients who have major surgery or significant traumatic injury within 28 days of the first dose of study treatment are not eligible. a. Central line placement or subcutaneous port placement is not considered major surgery. External central lines must be placed at least 3 days prior to enrollment and subcutaneous ports must be placed at least 7 days prior to enrollment. For further details regarding exclusion criteria please refer to the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 To determine MTD and/or RP2D of surufatinib, and to evaluate the safety and tolerability of surufatinib in combination with gemcitabine in pediatric patients with recurrent or refractory solid tumors or lymphoma Part 2 To evaluate the DCR in pediatric patients with osteosarcoma and the ORR in pediatric patients with Ewing sarcoma and RMS, NRSTS and other tumor types as per emerging data from part 1 of the study, when treated with the combination of surufatinib and gemcitabine;Secondary Objective: Part 1 To characterize the PK of surufatinib as a monotherapy and in combination with gemcitabine in pediatric patients To document the PK exposure of gemcitabine when used in combination with surufatinib To evaluate the anti-tumor activity of surufatinib in combination with gemcitabine in pediatric patients Acceptability and palatability of surufatinib oral suspension Part 2 To evaluate other anti-tumor activity of the combination of surufatinib and gemcitabine in pediatric patients as per emerging data from part 1 of the study To evaluate the safety and tolerability of surufatinib in combination with gemcitabine in pediatric patients as per emerging data from part 1 of the study To characterize the PK of surufatinib and in combination with gemcitabine in pediatric patients as per emerging data from part 1 of the study To document the PK exposure of gemcitabine when used in combination with surufatinib Acceptability and palatability of surufatinib oral suspension;Primary end point(s): Part 1 • The incidence of dose limiting toxicities in each dose level • Safety, as assessed by: o The frequency and severity of AEs o Physical examination findings o Vital signs o Laboratory test results o 12-lead ECG Part 2 • DCR at 16 weeks for patients with osteosarcoma • ORR at 14 weeks for patients with Ewing sarcoma, RMS, and NRSTS;Timepoint(s) of evaluation of this end point: Part 1: Dose Limiting Toxicity: Cycle 1 (35 days) Safety: from date of consent to 30 da | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 • Observed plasma concentrations of surufatinib and estimated population PK and exposure parameters for surufatinib • Pharmacokinetic parameters for the dose escalation and PK expansion cohorts: Cmax, Tmax, AUC, Cmin, effective T1/2, CL/F, and accumulation ratio • Observed plasma concentrations of gemcitabine • Efficacy endpoints evaluated per RECIST version 1.1: o ORR o DCR o TTR o Duration of response (DoR) o PFS • The taste and palatability survey Part 2 • TTR • DoR • PFS • Safety, as assessed by: o Frequency and severity of AEs o Physical examination findings o Vital signs o Laboratory test results o 12-lead ECG • Observed plasma concentrations of surufatinib and estimated population PK and exposure parameters for surufatinib • Observed plasma concentrations of gemcitabine • The taste and palatability survey;Timepoint(s) of evaluation of this end point: Part 1: Surufatinib PK: from Cycle 1 to last cycle Gemcitabine PK: Cycle 1 Efficacy: from start of treatment till the end of treatment The taste and palatability survey: C1D1 and C1D8 Part 2: Efficacy and Safety: from start of treatment till the end of treatment Taste survey: C1D1 and C1D8 Surufatinib PK: from Cycle 1 to last cycle Gemcitabine PK: Cycle 1 The taste and palatability survey: C1D1 and C1D8 | — |
Countries
Denmark, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactMark Woods
HUTCHMED Limited
Outcome results
None listed