Surufatinib Combined With Gemcitabine Plus Nab-paclitaxel in Locally Advanced Pancreatic Cancer

NCT06361030 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: HMPL-012-C2-PC01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of surufatinib combined with gemcitabine plus nab-paclitaxel in patients with locally advance d pancreatic cancer

Conditions

Pancreatic Cancer; Pancreatic Cancer Non-resectable; Pancreatic Ductal Adenocarcinoma, PDAC

Keywords

Pancreatic ductal adenocarcinoma; surufatinib; surgical conversion; gemcitabine; nab-paclitaxel

Outcome Measures

Primary Outcomes (1)

• Surgical conversion rate

  Surgical conversion rate, defined as the proportion of patients who achieved gross complete resection after 4-6 cycles of study induction therapy.

  Time from the first treatment up to 24 weeks

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  through study completion, an average of 1 year

• Disease control rate (DCR)

  through study completion, an average of 1 year

• R0 surgical conversion rate

  Time from the first treatment up to 24 weeks

• progression free survival(PFS)

  From date of the first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• Overall Survival (OS)

  Survival was followed (every 60±7 days ) up to 24 months after the end of treatment

Study Arms (1)

Experimental Group

EXPERIMENTAL

After 4-6 cycles of induction therapy with gemcitabine and nab-paclitaxel plus surufatinib, if become operable, the therapy will be continued for another 6 months after surgery; if not operable, the therapy will be also continued as long as no PD during induction therapy. If PD occurs, it will enter second-line therapy.

Drug: surufatinib combined with gemcitabine plus nab-paclitaxel

Interventions

surufatinib combined with gemcitabine plus nab-paclitaxel DRUG

Surufatinib capsules: oral, once daily. Combination treatment period: 200 mg each time, every 4 weeks for a treatment cycle(Q4W). If all the chemotherapy drugs were stopped during the maintenance treatment period, only surufatinib was left, the dose of Surufatinib could be increased to 300 mg per dose according to the patient\'s condition. Gemcitabine: iv, 1000 mg/m2, days 1, 8, and 15 of each treatment cycle, Q4W. Paclitaxel (albumin-bound), iv, 125mg/m2, on days 1, 8 and 15 of each treatment cycle, Q4W. All they will be used until disease progression, death, intolerable toxicity, initiation of new antineoplastic therapy, withdrawal of consent, loss to follow-up, or any other protocol-specified event requiring treatment discontinuation or study closure, whichever occurred first. But If surgical resection was performed, they will be only maintained for 6 months after surgery.

Experimental Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up;
• Aged 18-75 years old (including 18 and 75 years old)
• male or female
• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Unresectable pancreatic cancer according to radiographic criteria (CT or MRI scans) or exploration( NCCN guidelines were referred): (1)The portal and superior mesenteric vein could not be reconstructed safely due to tumor invasion, venous occlusion, or involvement of a large area of the superior mesenteric vein jejunal branch (2)If pancreatic head/uncinate tumor: tumor contacts superior mesenteric artery or celiac trunk artery \>180 degrees. If pancreatic body tail tumor: tumor contacts the superior mesenteric artery or celiac trunk artery\>180 degrees, and tumor contacts the celiac trunk artery and infiltrates the abdominal aorta.
• Without distant metastasis as defined by CT or MRI scan of the chest, abdomen and pelvis
• No prior systematic treatment for advanced pancreatic cancer
• At least one measurable lesion was required. (Response evaluation criteria in Solid Tumors, RECIST, version 1.1)
• ECOG performance status of 0 or 1
• Expected survival ≥12 weeks
• Acceptable organ and bone marrow function, laboratory values within 7 days prior to enrollment (no blood components, cell growth factors, albumin, or other corrective medications were allowed within 14 days prior to laboratory testing), as follows: (1)Blood routine: neutrophils ≥ 1.5 x 10⁹/L, platelets ≥ 100 x 10⁹/L, hemoglobin ≥ 9.0g/dL; (2) Liver function: serum total bilirubin ≤ 1.5 x ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 × ULN in subjects without liver metastases, AST and ALT levels ≤5 × ULN in subjects with documented liver metastases; (3) Renal function: serum creatinine ≤ 1.5 x ULN, or creatinine clearance (CCr) ≥ 50mL/min; Urine protein \< 2 +; if urine protein ≥2+ at baseline, 24-hour urine collection should be done and 24-hour urine protein \< 1g; (4) Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN.
• Female subjects of childbearing potential or male subjects whose sexual partner is a female of childbearing age should take effective contraceptive measures during the whole treatment period and 6 months after the last treatment.

You may not qualify if:

• Participants had a second primary malignancy detected prior to the first dose of study treatment, or has other malignancies diagnosed within 5 years prior to the first dose of study treatment, with the exception of radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radically resected carcinoma in situ;
• Allergy to study medication or excipients
• With dysphagia or known malabsorption of drugs
• Have participated in any other drug clinical trial and received the corresponding trial drug within the previous 4 weeks. Or are participating in other clinical studies that may interfere with this study.
• Drug-uncontrolled hypertension；systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg; History of hypertensive crisis or hypertensive encephalopathy.
• Patients with active gastric or duodenal ulcer, ulcerative colitis, intestinal obstruction, other gastrointestinal diseases, or active bleeding from unresectable tumors before enrollment, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigator; Or have a history of bowel perforation or fistula and do not fully recover from surgery.
• Patients had a history of arterial or deep-vein thrombosis within 6 months before enrollment ，or had evidence or history of bleeding tendency, regardless of severity, within 2 months before enrollment.
• Stroke or transient ischemic attack occurred within 12 months before enrollment.
• Incomplete healing of skin wounds, surgical sites, trauma sites, severe mucosal ulcers, or fractures.
• Active bacterial, viral, or fungal infections requiring systemic treatment, defined as signs/symptoms associated with the infection that persist and do not improve despite appropriate antibiotic, antiviral, and/or other treatments
• Known hepatitis B or C infection or a history of human immunodeficiency virus (HIV) infection ; Subjects receiving immunosuppressive or myelosuppressive drugs is considered to be associated with an increased risk of severe neutropenia complications by the investigators.
• Severe cardiovascular disease, including unstable angina or myocardial infarction, occurred within 6 months before enrollment; Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months before enrollment; New York Heart Association (NYHA) classification of congestive heart failure \>Grade 2; Ventricular arrhythmias requiring medical therapy; LVEF(left ventricular ejection fraction)\<50%. Electrocardiogram (ECG) corrected QT interval ≥480 msec.
• Clinically significant ascites
• Clinically significant electrolyte disturbances.
• Severe mental illness that may compromise the safety of the subjects or the integrity of the study data.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Anophthalmia with pulmonary hypoplasia

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Heshui Wu

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heshui Wu

CONTACT

+86 137-2011-7761; heshuiwu@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2024
• First Posted: April 11, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 11, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)