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History of Changes for Study: NCT04169672
Phase II Study of Surufatinib Combined With Toripalimab in Patients With Advanced Solid Tumors
Latest version (submitted August 29, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 18, 2019 None (earliest Version on record)
2 January 17, 2020 Recruitment Status, Study Status, Contacts/Locations and Study Identification
3 February 13, 2020 Contacts/Locations and Study Status
4 May 9, 2020 Study Status, Contacts/Locations, Eligibility, Outcome Measures, Arms and Interventions, Study Design and Study Description
5 August 29, 2021 Study Status, Arms and Interventions, Study Design, Study Description, Study Identification and Eligibility
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Study NCT04169672
Submitted Date:  November 18, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: 2019-012-00CH1
Brief Title: Phase II Study of Surufatinib Combined With Toripalimab in Patients With Advanced Solid Tumors
Official Title: A Phase II, Open-label, Single-arm, Multi-center Study of the Efficacy and Safety of Surufatinib Combined With Toripalimab in Patients With Advanced Solid Tumors
Secondary IDs:
Open or close this module Study Status
Record Verification: November 2019
Overall Status: Not yet recruiting
Study Start: December 12, 2019
Primary Completion: December 12, 2019 [Anticipated]
Study Completion: December 30, 2021 [Anticipated]
First Submitted: November 18, 2019
First Submitted that
Met QC Criteria:
November 18, 2019
First Posted: November 20, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
November 18, 2019
Last Update Posted: November 20, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hutchison Medipharma Limited
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: This is a phase II, single arm, open-label, multicenter study to evaluate the efficacy and safety of Surufatinib combined with Toripalimab in patients with advanced solid tumors.
Detailed Description: The study population is about 80 patients with advanced solid tumors, who fails or cannot tolerate standard therapies, or for whom no effective standard therapy is available, or who refuses standard therapies. Surufatinib 300 mg once a day (QD) will be orally administrated and Toripalimab 240mg will be intravenously administered every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. For Toripalimab, the upper time limit for treatment is 2 years. The primary objective is safety of safety run-in (about 6 patients) and objective response rate (ORR) of Surufatinib combined with Toripalimab in patients with advanced solid tumors.
Open or close this module Conditions
Conditions: Advanced Solid Tumors
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 80 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Surufatinib & Toripalimab
Surufatinib 300mg will be taken orally once daily continuously through a 21-day cycle of study treatment. Toripalimab 240mg will be intravenously administered on Day 1 of each cycle.
Drug: Surufatinib
Surufatinib is a tablet in the form of 50mg, oral, once a day.
Other Names:
  • HMPL-012
Drug: Toripalimab
Toripalimab is an injection in the form of 240mg, intravenous, once three weeks.
Other Names:
  • JS001
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Adverse events (AEs) of safety run-in part
[ Time Frame: From Cycle 1 Day 1 to the end of Cycle 2 Day 7 (each cycle is 21 days) ]

The AEs of the first 6 patients were evaluated by the possibly occurs Dose Limited Toxicity (DLT).
2. Objective response rate (ORR)
[ Time Frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy(up to approximately 2 years) ]

The incidence of confirmed complete response or partial response (RECIST1.1).
Secondary Outcome Measures:
1. Objective Response Rate (ORR)
[ Time Frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy(up to approximately 2 years) ]

The incidence of confirmed complete response or partial response (irRECIST).
2. Duration of Response (DoR) (RECIST1.1 and irRECIST)
[ Time Frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years) ]

Duration from the first time reported partial response or complete response to the first time of disease progression or death.
3. Progression-free Survival (PFS) (RECIST1.1 and irRECIST)
[ Time Frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years) ]

A duration from the date of initial treatment with Surufatinib combined with Toripalimab to disease progression or death of any cause.
4. Disease Control Rate (DCR) (RECIST1.1 and irRECIST)
[ Time Frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years) ]

Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.
5. Overall Survival (OS)
[ Time Frame: From date of first dose of study drug until withdrawal of consent or death (up to approximately 2 years) ]

Duration from the date of initial treatment with Surufatinib plus toripalimab to the date of death due to any cause.
6. The AEs of all population
[ Time Frame: For each participant, from the first participant first dose until 30 days after the last dose (up to approximately 2 years) ]

An AE is any untoward medical occurrence in a patient or clinical investigation participant administered an investigational product.Safety and tolerance evaluated by incidence, severity and outcomes of AEs
7. Anti-drug Antibody (ADA) of Toripalimab
[ Time Frame: half of hour predose of Toripalimab for Cycle 1, 2, 3, 4, 5 (each cycle is 21 days) and 336 hours after the last dose ]

Blood samples will be collected and analyzed. Serum ADA will be detected by using validated methods.
8. Plasma maximum Concentration (Cmax)
[ Time Frame: Surufatinib (Cycle 1 and 3): Day 1: predose;1, 2, 4, 8,12 and 24 hours postdose. Toripalimab (Cycle 1 and 3): predose; 0.5, 2, 6, 12,24,48,96,168,336 and 504 hours postdose ]

Blood samples will be collected at the designated time points.Cmax is the highest concentration of drug in the blood that is measured after a dose.
9. The drug concentration-time curve (AUC)
[ Time Frame: Surufatinib (Cycle 1 and 3): Day 1: predose;1, 2, 4, 8,12 and 24 hours postdose. Toripalimab (Cycle 1 and 3): predose; 0.5, 2, 6, 12,24,48,96,168,336 and 504 hours postdose ]

Plasma samples will be collected at the designated time points. AUC represents the overall amount of drug in the bloodstream after dosing.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Adequately understand the study and voluntarily sign the Informed Consent Form;
  • 18-75 years old;
  • Histologically or cytologically confirmed advanced solid tumors (focusing on neuroendocrine neoplasmas (NENs), biliary tract cancer, gastric cancer, thyroid cancer, small cell lung cancer, soft tissue sarcoma, and endometrial cancer);
  • Fail or cannot tolerate the standard therapies, or for whom no effective standard therapy is available, or refuse standard therapy;
  • Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale;
  • Have measurable lesions (according to RECIST 1.1);
  • Agree to provide histology samples;
  • Lab tests within 7 days before first dose:
    1. Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥100×10^9/L, and hemoglobin ≥9 g/dL;
    2. Serum total bilirubin <1.5 times the upper limit of normal (ULN);
    3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤ 1.5 times the ULN without liver metastases; and ALT and AST ≤ 3 times ULN with liver metastases;
    4. Serum creatinine <1.5 times ULN and creatinine clearance ≥50 mL/min;
    5. Urine protein < 2+; if ≥2+, 24-hour urine protein <1 g;
    6. International Normalized Ratio (INR) ≤1.5 ULN and activated partial thromboplastin time (APTT) ≤1.5 ULN;
  • Have expected survival of more than 12 weeks;
  • Male or females patients with reproductive potential must agree to use an effective contraceptive method, for example, double-barrier device, condom, oral or injected birth control medication or intrauterine device, during the study and within 90 days after study treatment discontinuation. All female patients are considered to be fertile, unless the patient had natural menopause or artificial menopause or sterilization (such as hysterectomy, bilateral oophorectomy or ovarian irradiation).

Exclusion Criteria:

  • Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for hair loss or Grade ≤ 2 peripheral neurotoxicity caused by oxaliplatin);
  • Other malignancies diagnosed within the previous 5 years, except skin basal cell carcinoma or skin squamous cell carcinoma or cervical carcinoma in situ;
  • Central nervous system metastases;
  • Systematic anti-tumor therapy received within 4 weeks prior to first dose, including chemotherapy, biotherapy, targeted therapy, hormonotherapy, and anti-tumor Chinese medicine treatment;
  • Radical radiotherapy within 4 weeks prior to first dose, radioactive seed implantation within 60 days prior to first dose, or Palliative radiotherapy for a bone metastasis lesion within 1 week prior to first dose;
  • Functional NENs which need to be treated with long acting Somatostatin analogues (SSAs) to control disease related syndromes, such as insulinoma, gastrinoma, glucagonoma, somatostatinoma, ACTHoma, VIPoma, accompanied by carcinoid syndrome, Zollinger-Ellison syndrome or other active symptoms;
  • Previously treated with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, anti-CTLA-4 antibody, any other antibody acting on the T cell stimulation or checkpoint pathway or Surufatinib;
  • Previously received anti-VEGF/VEGFR targeted drugs and progressed during the treatment or within 4 months after these drugs;
  • Thyroid dysfunction with symptoms or clinical significance when screening except hypothyroidism controlled only by thyroid hormone replacement therapy;
  • Previously received immunosuppressive drugs except locally or temporarily used glucocorticoids;
  • Autoimmune disease with systematic treatment or autoimmune disease history within 2 years;
  • Previously received systematic immunologic stimulants within 4 weeks;
  • Inoculated with any live vaccine or attenuated live vaccine within 4 weeks or planed to inoculate during the study;
  • Major surgery within 4 weeks or unhealed wound/ulcer/fracture;
  • Uncontrolled malignant hydrothorax, ascites, or pericardial effusion;
  • Under anti-hypertension treatment, still uncontrolled hypertension, defined as: systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg;
  • Disease or situation that affects drug absorption, or unable to take drugs orally;
  • Previously received CYP3A4 strong inducers or strong inhibitors within 1 week or 5 half-life periods;
  • Active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumor with active bleeding, or other gastrointestinal conditions that may cause bleeding or perforation by investigator's discretion;
  • History or presence of a serious hemorrhage (>30 ml within 2 months), hemoptysis (>5 ml blood within 4 weeks) within 2 months;
  • History or presence of an artery thrombosis or deep venous thrombosis within 6 months, or a thromboembolic event (including transient ischemic attack) within 12 months;
  • Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to first dose, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure according to the New York Heart Association (NYHA) classification ≥ 2; ventricular arrhythmias which needs drug treatment; left ventricular ejection fraction (LVEF) <50%;
  • Severe electrolyte abnormalities with clinical significance by investigator's discretion;
  • Any clinically significant active infection, or unknown reason fever prior to first dose (temperature > 38.5℃);
  • Active tuberculosis, on treatment or previously received antituberculosis therapy within 1 year;
  • History or presence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia or severely injured lung function except radiation pneumonia in the radiotherapy area;
  • A positive immunodeficiency virus (HIV) test;
  • History of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive (copies ≥1×10^3/ml or > 200 IU/ml); known Hepatitis C virus (HCV) infection with HCV RNA positive (copies ≥1×10^3/ml); or liver cirrhosis, etc.;
  • Previously received investigational treatments unlisted in China within 4 weeks prior to first dose;
  • Women who are pregnant or lactating;
  • Previously allergic to any of the JS001 or Surufatinib ingredients, or monoclonal antibody;
  • Any other conditions are inappropriate for the use of the investigational products by investigator's discretion.
Open or close this module Contacts/Locations
Central Contact Person: Panfeng Tan
Telephone: +86 021 20671828
Email: panfengt@hmplglobal.com
Central Contact Backup: Songhua Fan
Telephone: +86 021 20673058
Email: songhuaf@hmplglobal.com
Study Officials: Lin Shen
Principal Investigator
Peking University Cancer Hospital & Institute
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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