Phase II Study Of Ibrutinib In Advanced Carcinoid And Pancreatic Neuroendocrine Tumors

Study Overview

Phase II Study of Ibrutinib in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors

This is a prospective phase II open-label trial, stratifying patients equally into two cohorts consisting of carcinoid tumors and pancreatic neuroendocrine tumors (pNETs). The purpose of this study is to test any good and bad effects of the study drug called Ibrutinib. The study population will consist of adult patients with histologically confirmed low to intermediate grade NETs of the GI tract, lungs and unknown primary (carcinoid tumors) or pNETs. All patients must be confirmed to have advanced disease. The study will enroll up to 51 patients in two cohorts (30 carcinoid and 21 pNET patients).

N/A

Carcinoid Tumors
Pancreatic NET

DRUG: Ibrutinib

MCC-18141

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-10-12	Results First Submitted 2019-08-16	Last Update Submitted that met QC Criteria 2020-09-09
First Submitted that Met QC Criteria 2015-10-12	Results First Submitted that Met QC Criteria 2019-09-10	Last Update Posted (ACTUAL) 2020-09-11
First Posted (ACTUAL) 2015-10-14	Results First Posted 2019-10-02	Last Verified 2020-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Ibrutinib Therapy Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)	DRUG: Ibrutinib Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdraw

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Ibrutinib Therapy

Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD)

DRUG: Ibrutinib

Ibrutinib will be administered orally once daily and each cycle will be defined as 4 weeks duration. Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdraw

Primary Outcome Measures	Measure Description	Time Frame
Overall Radiographic Response Rate (ORR)	Response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. For this study, measurable disease is defined as the presence of at least one measurable lesion. Measurable lesions must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of: 10 mm by CT scan (CT scan slice thickness no greater than 5 mm (when CT scans have slice thickness >5 mm, the minimum size should be twice the slice thickness); 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable); 20 mm by chest X-ray. Complete Response (CR): complete disappearance of all target lesions, confirmed by repeat assessments at no less than 4 weeks after the criteria for response are first met. Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter.	Up to 18 months

Secondary Outcome Measures	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression free survival at one year. PFS, determined as the time from administration of the initial dose of ibrutinib until objective tumor progression using RECIST, or death. Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm.	1 year
Overall Survival (OS)	Overall Survival determined from the time of drug administration to death from any cause.	Up to 24 months
Occurrence of Possibly Related Adverse Events (AEs)	Adverse events possibly related to study treatment with Ibrutinib. Safety and tolerability will be assessed according to the NIH/NCI Common TerminologyCriteria for Adverse Events version 4 (CTCAE v4).	Up to 18 months
Duration of Response	Duration of response, defined as time from first observation of an objective response which is subsequently confirmed, to first disease progression or death due to any cause.	Up to 18 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Locally unresectable or metastatic carcinoid or pancreatic neuroendocrine tumors (pNETs)
Measureable disease by Response Evaluation Criteria in Solid Tumors (RECIST)
Tumors must be histologically or cytologically proven and considered low or intermediate grade. Patients with high grade neuroendocrine carcinomas or small cell carcinomas are excluded from the study.
Evidence of progressive disease within 12 months of study entry
Allowed prior therapies include: a) Surgery (major surgery at least more than four weeks prior to baseline assessment); b) Locoregional therapy such as: chemoembolization, radio-embolization, radiofrequency ablation, radiotherapy as long as there is progressive measurable disease outside the area of locoregional therapy or there is progression in the previously treated areas; c) Any number of previous lines of systemic therapy. Last treatment before enrollment must have occurred more than 4 weeks for chemotherapy, 6 weeks for antibodies or more than 5 half-lives of prior tyrosine kinase inhibitors (TKIs) or small molecules.
Prior or concurrent therapy with somatostatin analogs is permitted for patients with secretory NET
All patients with gastroenteropancreatic NETs must have progressed on (or are intolerant of) prior somatostatin analog.
Patients with pancreatic NETs must have progressed on (or are intolerant of) either everolimus or sunitinib.
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Life expectancy 12 weeks or more
Adequate bone marrow function as shown by: absolute neutrophil count ≥ 1,000/mm^3, Platelets ≥ 100,000/mm^3, Hb > 10 g/dl
Adequate liver function as shown by: serum bilirubin ≤ 1.5 x ULN, and serum transaminases activity ≤ 2.5 x ULN, with the exception of serum transaminases (< 3 x ULN) if the patient has liver metastases
Adequate renal function as shown by serum creatinine ≤ 2 mg/dl
Women of childbearing potential must have a negative serum pregnancy test within 7 days of the administration of the first study treatment. Women must not be lactating. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study.
Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information.

High grade NET or small cell neuroendocrine carcinoma
Clinically apparent central nervous system metastases or carcinomatous meningitis
Known positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class III or IV cardiac disease as defined by the New York Heart Association (NYHA) functional classification
Requirement for anticoagulation with warfarin or similar vitamin K antagonists.
Requirement for treatment with a strong cytochrome P450 (CYP) 3A4/5
Prior antitumor therapy within 2 weeks of enrollment (with the exception of somatostatin analogs)
No other active malignancy within 3 years of enrolment except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years
Any medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib
Known hypersensitivity to ibrutinib or any component of the ibrutinib formulation
History of noncompliance to medical regimens or unwillingness to comply with the protocol
Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Pharmacyclics LLC.

Investigators

PRINCIPAL_INVESTIGATOR: Jonathan Strosberg, M.D., H. Lee Moffitt Cancer Center and Research Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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