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Solid TumorPhase 1/2NCT05093322

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

A Phase 1/2 study testing Surufatinib in combination with Gemcitabine in people with Solid Tumor and Lymphoma, run by Hutchmed at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 18 years
Conditions the study is for
Solid Tumor, Lymphoma, Osteosarcoma
What is being tested?
Surufatinib in combination with Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
11 sitesUnited States
Study dates
30 Nov 2021to 25 Apr 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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;
Show all 20Show fewer
  • 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.
  • Adequate cardiac function as indicated as defined in the current protocol.
  • 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.
  • Adequate BP control which is defined as a BP <95th percentile (≤ grade 1) for age, height, and sex.
  • 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.
  • Patient must meet all defined Inclusion criteria as defined in the current protocol.

Who cannot join

  • Patient must not meet any exclusion criteria as defined in the current protocol.
  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Childrens Hospital Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Hospital

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Surufatinib in combination with Gemcitabine
Medical subject headings
Lymphoma, Osteosarcoma, Sarcoma, Ewing, Rhabdomyosarcoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Surufatinib in combination with GemcitabineDrug

    Also called HMPL-012, sulfatinib in combination with Gemcitabine

    Surufatinib in combination with Gemcitabine

Study groups in NCT05093322
Study groupRoleWhat they receive
Part 1- Dose escalationExperimentalDose 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.
Receives: Drug: Surufatinib in combination with Gemcitabine
Part 2 - Dose expansionExperimentalOnce 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.
Receives: Drug: Surufatinib in combination with Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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.

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

  5. Number of Patients With Clinically Significant Laboratory Abnormalities

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

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

  6. 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.

    Measured: 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)

  1. Objective Response Rate (ORR)

    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.

    Measured: 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.

  2. Disease Control Rate (DCR)

    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.

    Measured: 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.

  3. Time to Response (TTR)

    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.

    Measured: 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.

  4. Duration of Response (DoR)

    The DoR was defined as the time from the first occurrence of PR or CR whichever came first, until disease progression or death.

    Measured: 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.

  5. Progression-Free Survival (PFS)

    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.

    Measured: 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.

  6. Number of Patients Who Performed Taste and Palatability Survey of Surufatinib

    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).

    Measured: Days 1 and 8 of Cycle 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2021
  2. Study start30 Nov 2021
  3. Primary completion25 Apr 2023
  4. Study completion25 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05093322
Sponsor's protocol ID
2020-012-GLOB2
Other IDs
2021-003602-41
Status last verified
May 2024
First submitted
20 Sep 2021
Last updated
7 Jun 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Surufatinib in combination with Gemcitabine in people with Solid Tumor and Lymphoma, run by Hutchmed at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05093322.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2024.

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