Carcinoid TumorsPhase 2NCT02575300
Phase II Study of Ibrutinib in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors
A Phase 2 study testing Ibrutinib in people with Carcinoid Tumors and Pancreatic NET, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoid Tumors, Pancreatic NET
- What is being tested?
- Ibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Oct 2015to 4 Nov 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
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).
- Conditions
- Carcinoid Tumors, Pancreatic NET
- Being tested
- Ibrutinib
- Keywords
- neuroendocrine tumors (NETs), gastroenteropancreatic NETs, pancreatic NETs, gastrointestinal (GI) tract NET, advanced carcinoid tumors
- Medical subject headings
- Carcinoid Tumor, Adenoma, Islet Cell, Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called IMBRUVICA®
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 withdrawal of consent.
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib Therapy | Experimental | Ibrutinib Initial Dose 560 mg by mouth (PO) every day (QD) Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 18 months
Secondary outcomes (4)
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.
Measured: 1 year
Overall Survival (OS)
Overall Survival determined from the time of drug administration to death from any cause.
Measured: 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).
Measured: 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.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2015 (estimated)
- Study start9 Oct 2015
- Primary completion26 Mar 2019
- Study completion4 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoid TumorsStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Responsible party
- Sponsor
- Investigators
- Jonathan Strosberg, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02575300
- Sponsor's protocol ID
- MCC-18141
- Status last verified
- Sep 2020
- First submitted
- 12 Oct 2015
- Last updated
- 11 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Ibrutinib in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT02575300
- Acronym / sponsor ID
- MCC-18141
- Conditions
- Carcinoid Tumors, Pancreatic NET
- Keywords
- neuroendocrine tumors (NETs), gastroenteropancreatic NETs, pancreatic NETs, gastrointestinal (GI) tract NET, advanced carcinoid tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Study start
- 9 Oct 2015 (actual)
- Primary completion
- 26 Mar 2019 (actual)
- Study completion
- 4 Nov 2019 (actual)
- First posted
- 14 Oct 2015 (estimated)
- Results
- Posted 2 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib Therapy | Experimental | Drug: IbrutinibIbrutinib Initial Dose 560 mg by mouth (PO) every day (QD) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: IMBRUVICA®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 withdrawal of consent. | Drug | Ibrutinib Therapy |
Primary outcome
Overall Radiographic Response Rate (ORR)
Time frame: Up to 18 months
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.
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: 1 year
Overall Survival (OS)
Time frame: Up to 24 months
Occurrence of Possibly Related Adverse Events (AEs)
Time frame: Up to 18 months
Duration of Response
Time frame: Up to 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Moffitt Cancer Center Clinical Trials websiteLink provided by the sponsor.
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GEP-NET, Gastroenteropancreatic Neuroendocrine Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Strosberg, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib in people with Carcinoid Tumors and Pancreatic NET, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Radiographic Response Rate (ORR) (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2020.