A Study of Surufatinib in Combination With Gemcitabine in Pediatric, Adolescent, and Young Adult Patients With Recurrent or Refractory Solid Tumors

NCT05093322 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2020-012-GLOB22021-003602-41
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Solid Tumor; Lymphoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)

Outcome Measures

Primary Outcomes (6)

• Number of Patients With Dose-Limiting Toxicities (DLT)

  A DLT was defined as any of following events that were attributable to study treatment (at least possibly related). Adverse events (AE) were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. * Any Grade 3 or greater nonhematological toxicity. * Grade 3 liver enzyme elevation. * Cases of Hy's law. * Any Grade 2 nonhematological toxicity that persisted for \>= 7 days. * Any Grade 4 hypertension. * Grade 3 corrected QT interval prolongation \> 500 millisecond. * Grade 4 thrombocytopenia for \> 7 days. * Grade 3 thrombocytopenia with clinically significant bleeding. * Grade 4 neutropenia that lasted for \> 7 days. * Myelosuppression that caused a delay of \> 7 days in the start of Cycle 2.

  From the first dose of study drug (Day 1) up to Day 35 of Cycle 1

• Number of Patients With Treatment Emergent Adverse Events (TEAEs) by Severity

  The AEs were graded using the NCI CTCAE version 5.0. The CTCAE displays Grades 1 through 5 where, Grade 1= mild, Grade 2= moderate, Grade 3= Severe, Grade 4= life-threatening consequences and Grade 5= death.

  From the first dose of study drug (Day 1) up to 30 + 7 days after the last dose of study drug, approximately 19 weeks

• Number of Patients With Clinically Significant Physical Examination Abnormalities

  Physical examination included patient height, weight, and general condition, as well as an examination of the head, heart, chest (including the lungs), abdomen, extremities, skin, lymph nodes, nervous system, and additional areas/systems as clinically indicated.

  From the first dose of study drug (Day 1) up to 30 + 7 days after the last dose of study drug, approximately 19 weeks

• Number of Patients With Clinically Significant Vital Signs Abnormalities

  Vital signs included systolic blood pressure (BP), diastolic BP, heart rate, height, weight, respiratory rate, and body temperature.

  From the first dose of study drug (Day 1) up to 30 + 7 days after the last dose of study drug, approximately 19 weeks

• Number of Patients With Clinically Significant Laboratory Abnormalities

  Blood and urine samples were collected to determine the clinical chemistry, hematology, and urinalysis laboratory abnormalities.

  From the first dose of study drug (Day 1) up to 30 + 7 days after the last dose of study drug, approximately 19 weeks

• Number of Patients With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities

  Standard 12-lead ECGs were performed after the patient rested for 5 to 10 minutes. The ECG parameters included heart rate, PR interval, RR interval, QT interval, QTcF, and QRS interval from the triplicate 12-lead ECG.

  From the first dose of study drug (Day 1) up to 30 + 7 days after the last dose of study drug, approximately 19 weeks

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  RECIST assessments performed at baseline (within 28 days before start of study treatment), Day 1 of Cycle 3 and until confirmed objective disease progression. Up to approximately 19 weeks.

• Disease Control Rate (DCR)

  RECIST assessments performed at baseline (within 28 days before start of study treatment), Day 1 of Cycle 3 and until confirmed objective disease progression. Up to approximately 19 weeks.

• Time to Response (TTR)

  RECIST assessments performed at baseline (within 28 days before start of study treatment), Day 1 of Cycle 3 and until confirmed objective disease progression. Up to approximately 19 weeks.

• Duration of Response (DoR)

  RECIST assessments performed at baseline (within 28 days before start of study treatment), Day 1 of Cycle 3 and until confirmed objective disease progression. Up to approximately 19 weeks.

• Progression-Free Survival (PFS)

  RECIST assessments performed at baseline (within 28 days before start of study treatment), Day 1 of Cycle 3 and until confirmed objective disease progression. Up to approximately 19 weeks.

Study Arms (2)

Part 1- Dose escalation

EXPERIMENTAL

Dose escalation study with sequential dose escalation of surufatinib in combination with gemcitabine. Patients with any recurrent or refractory solid tumors or lymphoma, who have a known or expected dysfunction of VEGFR-1, -2, and -3; FGFR-1; or CSF-1R pathways may be enrolled.

Drug: Surufatinib in combination with Gemcitabine

Part 2 - Dose expansion

EXPERIMENTAL

Once the MTD/RP2D has been determined in the part 1 portion of the study, the part 2 disease specific cohorts for patients with refractory or recurrent osteosarcoma, Ewing Sarcoma, and RMS and NRSTS will open for enrollment.

Drug: Surufatinib in combination with Gemcitabine

Interventions

Surufatinib in combination with Gemcitabine DRUG

Surufatinib in combination with Gemcitabine

Also known as: HMPL-012, sulfatinib in combination with Gemcitabine

Part 1- Dose escalation; Part 2 - Dose expansion

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: At time of study enrollment, patients must be
• For US Sites:
• Part 1 (including PK expansion cohort): ≥2 and \<18 years of age;
• Part 2: ≥2 and ≤18 years of age;
• For EU/UK Sites:
• Part 1 (including PK expansion cohort): from birth to \<18 years of age;
• Part 2: from birth to \<18 years of age (except as noted below);
• Note: Patients \<2 years of age will only be enrolled in Europe, however, enrollment of patients \<2 years of age will not begin until definitive juvenile animal toxicity data is available.
• Diagnosis:
• Part 1 - Patients with any recurrent or refractory solid tumors or lymphoma (not central nervous system \[CNS\]) that have a known or expected dysfunction of VEGFR 1, -2, and -3; FGFR-1, or CSF-1R pathways (based on literature) are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse.
• Part 2 - Recurrent or refractory osteosarcoma (US and EU), Ewing sarcoma (US and EU), RMS (US and EU), or NRSTS (EU only). Patients must have had histologic verification of malignancy at original diagnosis or relapse.
• Disease status: Patients must have measureable or evaluable disease for part 1 dose escalation; for part 2, patients must have measurable disease by RECIST version 1.1.
• Therapeutic options: Patient's current disease state must be one for which there is no known curative therapy.
• Performance level: Karnofsky ≥50 for patients ≥16 and \<18 years of age and Lansky ≥50 for patients \<16 years of age, Eastern Cooperative Oncology Group (ECOG) ≤2 for patients ≥18 years of age.
• Adequate organ and bone marrow function as defined in the current protocol.

You may not qualify if:

• Pregnant, breast feeding or planning on becoming pregnant.
• Patients is taking and prohibitive concomitant medications as outlined in the current protocol.
• Patients have an uncontrolled infection.
• Patients has had major surgery or significant traumatic injury within 28 days of the first dose.
• Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy and without clinical imaging evidence of SD for 14 days or longer.
• History of allergies to Surufatinib and/or Gemcitabine.

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (11)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Childrens Hospital Orange County

Orange, California, 92868, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Lymphoma; Osteosarcoma; Sarcoma, Ewing; Rhabdomyosarcoma; Sarcoma

Interventions

surufatinib; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Myosarcoma; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Nick Lawn
• Organization: HUTCHMED Limited

nickl@hutch-med.com

+44 7826 422448

Study Officials

• Josephine Haduong

  Children's Hospital of Orange County

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: 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.

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: October 26, 2021
• Study Start: November 30, 2021
• Primary Completion: April 25, 2023
• Study Completion: April 25, 2023
• Last Updated: June 7, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-05

Locations

US (11)