Cabozantinib and Lanreotide as Treatment for Gastroenteropancreatic Neuroendocrine Tumors

NCT05048901 | Recruiting Phase 1 DMC

• 1 other identifier: T2221
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 11

Brief Summary

This is an Open-Label Phase I/II Study of daily cabozantinib plus lanreotide every 4 w eeks to treat advanced G1-2 gastroentero-pancreatic neuroendocrine tumor (GEP-NET) patients who failed to one line or more than one line of small molecule kinase inhibitor or well-differentiated (W-D) G3 GEP-NET who failed to one line of small molecule kinase inhibitor or chemotherapy.

Conditions

Neuroendocrine Tumors,Gastroenteropancreatic

Outcome Measures

Primary Outcomes (2)

• to determine the maximal tolerated dose of cabozantinib

  The dose of maximal tolerated dose of carbozantinib combination of cabozantinib and lanreotide for the recommended dose in phase II study.

  Phase I last patient in has been treated for 28 days

• Progression free survival

  The date of first study treatment to the date of disease progression.

  The time from registration to occurrence of progression based on the tumor response assessment by scheduled or un- scheduled CT scan or MRI. (whichever occurs first assessed up to 72 months)

Secondary Outcomes (6)

• Response rate

  Every 8 weeks for first 4 cycles then every 3 cycles (12 weeks) until disease progress. (each cycle is 28 days)

• Overall survival

  The time from registration to death from any cause assessed up to 72 months.

• Toxicities

  Approximately 72 months.

• Genetic study

  Approximately 72 months.

• Somatic mutation

  Approximately 72 months.

Study Arms (1)

Cabozantinib and Lanreotide

EXPERIMENTAL

Oral cabozantinib 40-60 mg/day and lanreotide 120mg deep subcutaneous injection (SC) in day 1 every 4 weeks.

Drug: Cabozantinib; Drug: Lanreotide

Interventions

Cabozantinib DRUG

Oral Cabozantinib 40-60 mg daily .every 4 weeks as a cycle

Also known as: Cabometyx

Cabozantinib and Lanreotide

Lanreotide DRUG

Lanreotide 120 mg deep SC on day 1 every 4 weeks.every 4 weeks as a cycle

Also known as: Somatuline

Cabozantinib and Lanreotide

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed G1 or G2 NET of GEP origin with locally advanced or metastatic stage who failed to one line or more than one line of small molecular kinase inhibitor (mTOR inhibitor or other targeted kinase inhibitor) or W-D G3 NET of GEP origin with locally advanced or metastatic stage who failed to one line or more than one line of chemotherapy or small molecule kinase inhibitor.
• Radiologic progression within 12 months of entry
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
• Age≥ 20 years old and ECOG Performance Status ≤ 1.
• Adequate organ and marrow function, based upon meeting all the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony- stimulating factor support.
• White blood cell count ≥ 2500/µL.
• Platelets ≥ 100,000/µL without transfusion.
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). If there is liver metastasis, AST, ALT ≤ 5 x ULN. ALP ≤ 5 x ULN with documented bone metastases.
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
• Serum albumin ≥ 2.8 g/dl
• (PT)/INR or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation:
• Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] ×72)\] × 0.85

You may not qualify if:

• Prior use of cabozantinib. (prior use of lanreotide is acceptable)
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer, before first dose of study treatment.
• Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before first dose of study treatment.
• Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
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• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:

Sponsors & Collaborators

• National Taiwan University Hospital: collaborator
• Taipei Veterans General Hospital, Taiwan: collaborator
• Mackay Memorial Hospital: collaborator
• Tri-Service General Hospital: collaborator
• Changhua Christian Hospital: collaborator
• China Medical University Hospital: collaborator
• National Cheng-Kung University Hospital: collaborator
• Kaohsiung Medical University Chung-Ho Memorial Hospital: collaborator
• Taichung Veterans General Hospital: collaborator
• National Health Research Institutes, Taiwan: lead

Study Sites (11)

Changhua Christian Hospital

Changhua, Taiwan

RECRUITING

Chang Gung Medical Foundation

Kaohsiung City, Taiwan

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

RECRUITING

China Medical University Hospital

Taichung, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, Taiwan

RECRUITING

National Cheng Kung University Hospita

Tainan, Taiwan

RECRUITING

Mackay Memorial Hospital

Taipei, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, Taiwan

RECRUITING

Tri-Service General Hospital

Taipei, Taiwan

RECRUITING

Chang Gung Medical Foundation

Taoyuan District, Taiwan

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

cabozantinib; lanreotide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Hui-Jen Tsai, PhD

  National Health Research Institutes, Taiwan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ya-Ling Wu, BS

CONTACT

886-3-7206166; yalin@nhri.edu.tw

Hui-Jen Tsai, PhD

CONTACT

886-6-2353535; hjtsai@nhri.org.tw

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: September 17, 2021
• Study Start: September 17, 2021
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 9, 2026

Record last verified: 2025-12

Locations

TW (11)