Carcinoid TumorPhase 2NCT02399215
Nintedanib in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors
A Phase 2 study testing Laboratory Biomarker Analysis, Nintedanib and Pharmacological Study in people with Carcinoid Tumor and Metastatic Carcinoid Tumor, run by Roswell Park Cancer Institute at 2 sites in United States.
Trial summary
This phase II trial studies how well nintedanib works in treating patients with neuroendocrine tumors that have spread from where they started to nearby tissue or lymph nodes (locally advanced) or have spread from the primary site (place where they started) to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoid Tumor, Metastatic Carcinoid Tumor, Neuroendocrine Neoplasm
- What is being tested?
- Laboratory Biomarker Analysis, Nintedanib and Pharmacological Study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 May 2015to 31 Aug 2022
- 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
- Patient must be on a stable dose of octreotide (Sandostatin®) long-acting release (LAR) or lanreotide for 3 months prior to study enrollment
- Patient must have histologically or cytologically confirmed well differentiated or moderately differentiated (low grade or intermediate grade) neuroendocrine tumor that is locally advanced or metastatic and not of pancreatic origin
- Measurable disease determined by computed tomography (CT) or magnetic resonance imaging (MRI)
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Life expectancy greater than 3 months
- Leukocytes >= 3,000/uL
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- Absolute neutrophil count >= 1,500/uL
- Total bilirubin =< 2 mg/dL
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN) and bilirubin =< ULN for patients without liver metastases
- AST/ALT =< 2.5 x ULN and bilirubin =< ULN for patients with liver metastases
- Patients with Gilbert syndrome and bilirubin < 2 x ULN and normal AST/ALT
- Creatinine =< 1.5 mg/dl
- Prior treatment will be permitted including surgery (>= 4 weeks), cytotoxic chemotherapy (maximum of 2 prior regimens); radiation, interferon, targeted growth factors (>= 4 weeks); and prior treatment with octreotide, will be allowed
- Ability to swallow and retain oral medication
- Participants of child-bearing potential (both male and female) must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
- Archival tissue of carcinoid biopsy must be available
Who cannot join
- Uncontrolled hypertension, unstable angina, New York Heart Association grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication, or clinically significant peripheral vascular disease (grade II or greater)
- Presence of brain metastases
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, or anticipated need for major surgical procedure during the course of the study, or fine needle aspirations or core biopsies within 7 days prior to day 0
- Significant proteinuria at baseline (>= 500 mg/24 hours [h])
- Serious non-healing wound, ulcer or bone fracture
- Evidence of bleeding diathesis or coagulopathy
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- Recent (=< 6 months) arterial thromboembolic events, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarction
- Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoma, or small cell carcinoma
- Hepatic artery embolization or ablation of hepatic metastasis within 3 months of enrollment, prior peptide receptor radionuclide therapy (PRRT) within 4 months or any other cancer therapy within 4 weeks (as long as all toxicities are resolved)
- Intolerance or hypersensitivity to octreotide
- Severe or uncontrolled medical conditions
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or nursing female participants
- Unwilling or unable to follow protocol requirements
- Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: Multicenter Phase 2 Study of Nintedanib for Patients With Advanced Carcinoid Tumors
This phase II trial studies how well nintedanib works in treating patients with neuroendocrine tumors that have spread from where they started to nearby tissue or lymph nodes (locally advanced) or have spread from the primary site (place where they started) to other places in the body (metastatic). Nintedanib may stop the growth of tumor cells by slowing or stopping a certain type of receptor called vascular endothelial growth factor receptor (VEGFR) from attaching to its target. This may stop the growth of neuroendocrine tumors by blocking the growth of new blood vessels necessary for tumor growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess progression free survival (PFS), defined as the time interval from initiation of therapy, to its cessation for documentation of progressive disease (PD) or death.
SECONDARY OBJECTIVES:
- To assess the clinical response (complete response + partial response) in all patients with measurable disease (using standard Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 criteria).
II. To assess overall survival (OS) in all patients. III. Assess changes in quality of life (QOL) throughout treatment using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) - Gastrointestinal Neuroendocrine Tumors (NET) 21 (GI.NET21) questionnaire for carcinoid patients with gastrointestinal neuroendocrine tumors, in all patients who have filled out at least two QOL questionnaires and, will be reported by groups based on response (response, stable disease or progressive disease).
IV. Steady-state pharmacokinetics (PK) of nintedanib, biomarkers, regulatory T cell (Treg) and cytokine expression and growth factors will be analyzed for all patients and reported in groups based on response.
- Gene mutations and copy number alterations analysis in the mammalian target of rapamycin (mTOR) pathway (will be performed only on the first 10 patients), protein expression of activation of protein kinase B (Akt) (as well as other downstream targets).
VI. Toxicity (graded using the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) will be closely monitored and all toxicities will be tabulated.
OUTLINE:
Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.
- Being tested
- Laboratory Biomarker Analysis, Nintedanib, Pharmacological Study, Quality-of-Life Assessment
- Medical subject headings
- Carcinoid Tumor, Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
NintedanibDrug
Also called BIBF 1120, BIBF-1120, Intedanib, Multitargeted Tyrosine Kinase Inhibitor BIBF 1120
Given PO
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (nintedanib) | Experimental | Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Nintedanib; Other: Pharmacological Study; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Will be reported using standard Kaplan-Meier methods. Ninety percent confidence intervals for the median PFS will be calculated using Greenwood's formula. Additionally, a confidence interval for the 16-week PFS rate will be obtained using Jeffrey's prior method. The association between survival and quantified variables will be investigated using the Cox-proportional hazard model.
Measured: Time interval from initiation of therapy, to its cessation for documentation of PD or death, assessed up to 2 years
Secondary outcomes (5)
Change in Quality of Life Score
Quality of life will be investigated calculated by Subjects filing out EORTC Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21) A 21 question questionnaire that use a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much). The scores for different scales (i.e. endocrine, gastrointestinal, treatment, social function, disease Related, and global) are calculated by summing related questions from the questionnaire. The range of the subscale scores are from 0 to 100, with higher scores being worse.
After the subscale scores being calculated, the Change in quality of life is calculated by subtracting baseline score from end of treatment
Measured: Baseline to 30 days post-treatment
Plasma Concentrations at Steady State (Cpre,ss) of Nintedanib at Baseline and Week 8
Sample collection will be obtained at baseline and week 8
Measured: Baseline to week 8
Clinical Response (Complete Response + Partial Response) Measured Using Standard RECISTv1.1 Criteria
Exact 90% confidence interval estimates using the Clopper-Pearson method will be given for the response rates. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI, response rates are categorized as Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 2 years
Median OS
Will be reported using standard Kaplan-Meier methods. Ninety-five percent confidence intervals for the median OS will be calculated using Greenwood's formula. The association between survival and quantified variables will be investigated using the Cox-proportional hazard model.
Measured: Up to 3 years (telephone contact is acceptable).
Ratio of FGFR IIIb/IIIc and Ki-67 and Microvessel Density Scores
Scores will be obtained to investigate association with PFS, clinical response, QOL and survival.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2015 (estimated)
- Study start15 May 2015
- Primary completion1 Sep 2019
- Study completion31 Aug 2022
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 TumorStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer 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
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Responsible party
- Sponsor
- Investigators
- Renuka Iyer, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02399215
- Sponsor's protocol ID
- I 259114
- Other IDs
- NCI-2015-00238, I 259114
- Status last verified
- Dec 2023
- First submitted
- 13 Mar 2015
- Last updated
- 26 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase 2 Study of Nintedanib for Patients With Advanced Carcinoid Tumors
- ClinicalTrials.gov ID
- NCT02399215
- Acronym / sponsor ID
- I 259114
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Study start
- 15 May 2015 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 26 Mar 2015 (estimated)
- Results
- Posted 28 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well nintedanib works in treating patients with neuroendocrine tumors that have spread from where they started to nearby tissue or lymph nodes (locally advanced) or have spread from the primary site (place where they started) to other places in the body (metastatic). Nintedanib may stop the growth of tumor cells by slowing or stopping a certain type of receptor called vascular endothelial growth factor receptor (VEGFR) from attaching to its target. This may stop the growth of neuroendocrine tumors by blocking the growth of new blood vessels necessary for tumor growth.
Detailed description
PRIMARY OBJECTIVES:
- To assess progression free survival (PFS), defined as the time interval from initiation of therapy, to its cessation for documentation of progressive disease (PD) or death.
SECONDARY OBJECTIVES:
- To assess the clinical response (complete response + partial response) in all patients with measurable disease (using standard Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 criteria).
II. To assess overall survival (OS) in all patients. III. Assess changes in quality of life (QOL) throughout treatment using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) - Gastrointestinal Neuroendocrine Tumors (NET) 21 (GI.NET21) questionnaire for carcinoid patients with gastrointestinal neuroendocrine tumors, in all patients who have filled out at least two QOL questionnaires and, will be reported by groups based on response (response, stable disease or progressive disease).
IV. Steady-state pharmacokinetics (PK) of nintedanib, biomarkers, regulatory T cell (Treg) and cytokine expression and growth factors will be analyzed for all patients and reported in groups based on response.
- Gene mutations and copy number alterations analysis in the mammalian target of rapamycin (mTOR) pathway (will be performed only on the first 10 patients), protein expression of activation of protein kinase B (Akt) (as well as other downstream targets).
VI. Toxicity (graded using the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) will be closely monitored and all toxicities will be tabulated.
OUTLINE:
Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (nintedanib) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Nintedanib, Other: Pharmacological Study, Other: Quality-of-Life AssessmentPatients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patient must be on a stable dose of octreotide (Sandostatin®) long-acting release (LAR) or lanreotide for 3 months prior to study enrollment
- Patient must have histologically or cytologically confirmed well differentiated or moderately differentiated (low grade or intermediate grade) neuroendocrine tumor that is locally advanced or metastatic and not of pancreatic origin
- Measurable disease determined by computed tomography (CT) or magnetic resonance imaging (MRI)
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Life expectancy greater than 3 months
Key exclusion criteria (15 listed)
- Uncontrolled hypertension, unstable angina, New York Heart Association grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication, or clinically significant peripheral vascular disease (grade II or greater)
- Presence of brain metastases
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, or anticipated need for major surgical procedure during the course of the study, or fine needle aspirations or core biopsies within 7 days prior to day 0
- Significant proteinuria at baseline (>= 500 mg/24 hours [h])
- Serious non-healing wound, ulcer or bone fracture
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (nintedanib) |
| NintedanibAlso: BIBF 1120, BIBF-1120, Intedanib, Multitargeted Tyrosine Kinase Inhibitor BIBF 1120Given PO | Drug | Treatment (nintedanib) |
| Pharmacological StudyCorrelative studies | Other | Treatment (nintedanib) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (nintedanib) |
Primary outcome
PFS
Time frame: Time interval from initiation of therapy, to its cessation for documentation of PD or death, assessed up to 2 years
Will be reported using standard Kaplan-Meier methods. Ninety percent confidence intervals for the median PFS will be calculated using Greenwood's formula. Additionally, a confidence interval for the 16-week PFS rate will be obtained using Jeffrey's prior method. The association between survival and quantified variables will be investigated using the Cox-proportional hazard model.
5 secondary outcomes
Change in Quality of Life Score
Time frame: Baseline to 30 days post-treatment
Plasma Concentrations at Steady State (Cpre,ss) of Nintedanib at Baseline and Week 8
Time frame: Baseline to week 8
Clinical Response (Complete Response + Partial Response) Measured Using Standard RECISTv1.1 Criteria
Time frame: Up to 2 years
Median OS
Time frame: Up to 3 years (telephone contact is acceptable).
Ratio of FGFR IIIb/IIIc and Ki-67 and Microvessel Density Scores
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Renuka Iyer principal investigator
Roswell Park Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis, Nintedanib and Pharmacological Study in people with Carcinoid Tumor and Metastatic Carcinoid Tumor, run by Roswell Park Cancer Institute at 2 sites 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 17 inclusion and 15 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 26 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 28 Jun 2022). 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?
PFS (time frame: Time interval from initiation of therapy, to its cessation for documentation of PD or death, assessed up to 2 years). 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 26 Dec 2023.