A clinical trial aiming to assess the safety and activity of the combination of cabozantinib plus lanreotide in gastroenteropancreatic (GEP) and thoracic neuroendocrine tumor (NET)

Phase 1

• Conditions: gastroenteropancreatic (GEP) and thoracic neuroendocrine tumor (NET); MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-004506-10-IT
• Lead Sponsor: FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-20
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

Each patient must meet all of the following inclusion criteria to be enrolled in the study:
-voluntary written informed consent obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care;
-Patients with unresectable, advanced or metastatic neuroendocrine well differentiated GEP-NET (pancreatic NET (G2-G3), Small Intestinal NET, stomach NET, rectum NET) with Ki67 ¿ 10%.
-Patients with unresectable, advanced or metastatic neuroendocrine well differentiated thoracic NET (typical and atypical lung NET, thymus NET)
-Patients with unresectable, advanced or metastatic neuroendocrine well differentiated unknown primary NET with Ki67 ¿ 10%.
-Locally advanced or metastatic disease documented as progressive by RECIST v1.1. on CT-scan or MRI at baseline and within 12 months prior to baseline.
-disease that is not amenable to surgery with curative intent;
-presence of at least one measurable target lesion for further evaluation according to RECIST v1.1;
-age =18 years;
-eastern Cooperative Oncology Group (ECOG) performance status 0 or 1(see APPENDIX I)
-Octreoscan and/or PET 68Ga positive and/or IHC for SSTR2;
-advanced GEP, thoracic and unknown origin NET limited to treatment naïve patients or who have received maximum 1 prior systemic regimen for metastatic disease (biological therapy, chemotherapy or somatostatin analogs, including PRRT);
-Prior PRRT therapy must be completed at least 6 months prior to enrollement;
-Prior treatment with somatostatin analogs, biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, and/or radiation must be completed at least 28 days prior to registration;
-Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective internal radiation therapy) or ablative therapies must be completed at least 28 days prior to registration;
-Prior treatment with cabozantinib or lanreotide are not allowed;
-Patients should have resolution of any toxic effects of prior therapy (except alopecia and fatigue) to National Cancer Institute (NCI) CTCAE, version 5.0, grade 1 or less;
-Patients must have completed any major surgery at least 12 weeks prior to registration and any minor surgery (including uncomplicated tooth extractions) at least 28 days prior to registration; complete wound healing from major surgery must have occurred at least 28 days prior to registration, and complete wound healing from minor surgery must have occurred at least 10 days prior to registration
-Non-functioning tumors;
- all of the following laboratory test findings:
-Hemoglobin > 9 g/dL (5.6 mmol/L)
-WBC > 2,000/mm3
-Neutrophils > 1,500/mm3
-Platelets > 100,000/mm3
-AST or ALT < 3 x ULN (< 5 x ULN if liver metastases are present)
-Total Bilirubin < 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
-Serum creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance = 40 mL/min (measured or calculated by Cockroft-Gault formula)
-Lipase < 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis
-PT-INR/PTT = 1.5 x upper limit of normal.
-Availability of a representative FFPE tumor specimen collected before starting treatment with cabozantinib and lanreotide that enables the definitive diagnosis of NET (the archival speci

Exclusion Criteria

-Patients with undifferentiated, poorly differentiated GEP-NET, Thoracic or unknown primary NET;
-Previous therapy for advanced disease > 1 line; any medical adjuvant treatment must have been stopped at least six months before entry into the study;
-Prior treatment with dose superior or equal to 120 mg per month of lanreotide;
-Prior treatment with cabozantinib;
-Prior treatment with any other tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors is permitted. Prior treatment with non-VEGF-targeted angiogenic inhibitors such as Everolimus is permitted;
-Patients who stopped Everolimus or tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors treatment less than 4 weeks prior to the start of the study;
-Patients with concomitant treatment with Interferon;
-Patients previously treated with chemotherapy, loco-regional therapy (e.g., chemoembolization) or interferon with last administration less than 4 weeks prior to the start of the study or with toxicity not resolved to less or equal grade 1 at the start of the study;
-PRRT therapy with last administration less than 6 months prior to inclusion in the study or with toxicity not resolved to less or equal grade 1 at the start of the study;
-diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri;
-history of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA see Appendix II);
-history of aneurysms and arterial dissections. The use of VEGF pathway inhibitors in patients with or without hypertension may favor the formation of aneurysms and / or arterial dissections. Before starting cabozantinib, this risk must be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
-poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg];
-history of cerebrovascular accidents, including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible;
-concomitant anticoagulation at therapeutic doses with oral anticoagulant (eg. Warfarin, direct thrombin and factor 10a inhibitors) or platelet inhibitors (eg. Clopidrogrel);
-major surgery or trauma within 28 days prior to study entry; the presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement are not considered to be major surgery);
-known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before the start of the study. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of inclusion;
- With the exclusion of inhaled steroids, chronic treatment with corticosteroids with dose superior of 10 mg/day methylprednisolone equivalent must be avoided;

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified