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

May 23, 2024 updated by: Hutchmed

An Open-Label, Multicenter Phase 1/2 Study of Surufatinib in Combination With Gemcitabine in Pediatric, Adolescent, and Young Adult Patients With Recurrent or Refractory Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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-rhabdomyosarcoma soft tissue sarcoma (NRSTS).

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-rhabdomyosarcoma soft tissue sarcoma (NRSTS)).

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
No longer available

No longer available

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • California
      • Orange, California, United States, 92868
        • Childrens Hospital Orange County
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • UPMC Children's Hospital of Pittsburgh
    • Texas
      • Dallas, Texas, United States, 75390
        • The University Of Texas Southwestern Medical Center
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age: At time of study enrollment, patients must be

    For US Sites:

    1. Part 1 (including PK expansion cohort): ≥2 and <18 years of age;
    2. Part 2: ≥2 and ≤18 years of age;

    For EU/UK Sites:

    1. Part 1 (including PK expansion cohort): from birth to <18 years of age;

    2. 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.

  2. Diagnosis:

    1. 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.
    2. 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.
  3. 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.
  4. Therapeutic options: Patient's current disease state must be one for which there is no known curative therapy.
  5. 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.
  6. Adequate organ and bone marrow function as defined in the current protocol.
  7. Adequate cardiac function as indicated as defined in the current protocol.
  8. Patients with known bone marrow metastatic disease will be eligible for the study provided they meet the blood counts in the inclusion criteria as defined in the current protocol.
  9. Adequate BP control which is defined as a BP <95th percentile (≤ grade 1) for age, height, and sex.
  10. Informed consent: Provision of signed and dated written informed consent (parent/legal guardian if patient <18 years of age) and assent (from patients aged >7 years) prior to any study-specific procedures, sampling, and analyses.
  11. Patient must meet all defined Inclusion criteria as defined in the current protocol.

Exclusion Criteria:

  1. Patient must not meet any exclusion criteria as defined in the current protocol.
  2. Pregnant, breast feeding or planning on becoming pregnant.
  3. Patients is taking and prohibitive concomitant medications as outlined in the current protocol.
  4. Patients have an uncontrolled infection.
  5. Patients has had major surgery or significant traumatic injury within 28 days of the first dose.
  6. 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.
  7. History of allergies to Surufatinib and/or Gemcitabine.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1- Dose escalation
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
Surufatinib in combination with Gemcitabine
Other Names:
  • HMPL-012, sulfatinib in combination with Gemcitabine
Experimental: Part 2 - Dose expansion
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
Surufatinib in combination with Gemcitabine
Other Names:
  • HMPL-012, sulfatinib in combination with Gemcitabine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Patients With Dose-Limiting Toxicities (DLT)
Time Frame: From the first dose of study drug (Day 1) up to Day 35 of Cycle 1

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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 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.
The ORR was defined as the percentage of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The BOR was defined as the best response recorded from the start of study treatment until documented RECIST version 1.1 progression, death, or withdrawal of consent. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
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)
Time Frame: 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.
The DCR was defined as the percentage of patients with a BOR of CR, PR, or stable disease as determined by the investigator using RECIST version 1.1. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study.
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)
Time Frame: 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.
The TTR was defined as the time from the start of study treatment until the date of the first occurrence of PR or CR for responders only.
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)
Time Frame: 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.
The DoR was defined as the time from the first occurrence of PR or CR whichever came first, until disease progression or death.
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)
Time Frame: 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.
The PFS was defined as the time from the start of study treatment until the first radiographic documentation of objective progression as assessed by the investigator using RECIST version 1.1 or death from any cause.
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.
Number of Patients Who Performed Taste and Palatability Survey of Surufatinib
Time Frame: Days 1 and 8 of Cycle 1
The taste and palatability survey was assessed in patients who had taken surufatinib oral suspension. For pediatric patients, their parents completed the taste and palatability survey. Data for the evaluation of taste of surufatinib oral suspension was summarized on a scale of 1 (very bad) through 5 (very nice).
Days 1 and 8 of Cycle 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hutchmed

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Josephine Haduong, Children's Hospital of Orange County

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 30, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 25, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 25, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 20, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 13, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 26, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 7, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 23, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020-012-GLOB2
  • 2021-003602-41 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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