A phase II study to evaluate the safety and efficacy of lenvatinib in patients with advanced grade 1/2 neuroendocrine neoplasmas of pancreatic and extrapancreatic origin.
- Conditions
- Patients with advanced/metastatic, histologically confirmed, grade 1/2 (G1/G2) of 2010 WHO classification neuroendocrine tumors of the pancreas after progression to a previous targeted agent (cohort A) or gastrointestinal tract after progression to somatostatin analogues (cohort B).MedDRA version: 21.0Level: LLTClassification code 10062476Term: Neuroendocrine tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10068909Term: Pancreatic neuroendocrine tumour metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-001467-39-IT
- Lead Sponsor
- GETNE (GRUPO ESPAñOL DE TUMORES NEUROENDOCRINOS)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 110
1.Subjects must have histologically confirmed diagnosis of one of the following advanced/metastatic neuroendocrine tumor types:
a)WHO Classification G1/G2 pancreatic neuroendocrine tumor
b)WHO Classification G1/G2 gastrointestinal neuroendocrine tumor (including stomach, small intestine and colorectal origins).
2.Subjects must have evidence of measurable disease meeting specific criteria;
3.Subjects must show evidence of disease progression by radiologic image techniques within 12 months prior to signing informed consent, according to RECIST 1.1 (Appendix I).
4.Subjects must meet the following inclusion criterion regarding primary tumor site:
a)Pancreatic origin;
b)Gastrointestinal origin;
5. Only for patients with pancreatic origin neuroendocrine tumors, one previous line with chemotherapy is allowed
6.Concomitant somatostatin analogues are allowed in both cohorts during the study.
7.Patients with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic and off of steroids for at least one month.
8.All prior chemotherapy or radiation-related toxicities must have resolved to < Grade 2 (following CTCAE V 4.03 grade levels), except alopecia and infertility.
9.Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 ? 1 (Appendix II).
10.Previous liver locoregional therapies, such as (chemo) embolization, radiofrequency or liver-directed radioembolization, or systemic peptide-receptor radionucleotide therapy are allowed if the procedure was performed at least 6 months previous the informed consent form signature.
11.Adequately controlled blood pressure with or without antihypertensive medications, defined as BP < 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
12.Adequate renal function defined as calculated creatinine clearance ? 30 mL/min per the Cockcroft and Gault formula (Appendix III).
13.Adequate bone marrow function.
14.Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) = 1.5. Prophylactic low molecular weight heparin therapy is allowed.
15.Adequate liver function.
16.Males or females age ? 18 years at the time of informed consent.
17. All females must have a negative serum or urine pregnancy test at the baseline visit. Females of childbearing potential must agree to use a highly effective method of contraception.
18.Male subjects who are partners of women of childbearing potential must use or their partners must use a highly effective method of contraception.
19.Voluntary provision of written informed consent and the willingness and ability to comply with all aspects of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55
1.WHO Classification G3 neuroendocrine tumors of the pancreas and gastrointestinal tract.
2.Two or more prior lines of targeted agents-based therapy in pancreatic origin and any previous line of targeted therapy for gastrointestinal origin or any ongoing antiproliferative treatment for advanced/metastatic neuroendocrine tumors, with the exception of somatostatin analogues therapy.
3.More than one previous line of chemotherapy in pancreatic neuroendocrine tumors.
4.Previous chemotherapy in gastrointestinal neuroendocrine tumors.
5.Prior treatment with lenvatinib.
6.Subjects who have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment. This does not apply to the use of somatostatin analogues for symptomatic therapy.
7.Major surgery within 3 weeks prior to the first dose of study drug.
8.Subjects having > 1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein = 1g/24h will be ineligible.
9.Gastrointestinal malabsorption, or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
10.Significant cardiovascular impairment.
11.Prolongation of QTcF interval to > 480 msec.
12.Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. Treatment with low molecular weight heparin (LMWH) is allowed.
13.Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
14.Active infection (any infection requiring treatment).
15.Active malignancy within the past 5 years.
16.Known intolerance or hypersensitivity to the active substance (or any of the excipients).
17.Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
18.Females who are pregnant or breastfeeding.
19.Documented active alcohol or drug abuse.
20.Patients with a prior history of non-compliance with medical regimens.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method