Nintedanib in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

NCT02399215 | Completed Phase 2 Results DMC

• 2 other identifiers: I 259114NCI-2015-00238
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief 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). 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.

Conditions

Carcinoid Tumor; Metastatic Carcinoid Tumor; Neuroendocrine Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Baseline to 30 days post-treatment

• Plasma Concentrations at Steady State (Cpre,ss) of Nintedanib at Baseline and Week 8

  Baseline to week 8

• Clinical Response (Complete Response + Partial Response) Measured Using Standard RECISTv1.1 Criteria

  Up to 2 years

• Median OS

  Up to 3 years (telephone contact is acceptable).

• Ratio of FGFR IIIb/IIIc and Ki-67 and Microvessel Density Scores

  Baseline

Other Outcomes (5)

• Biomarker Levels

  Baseline

• Change in Cytokine Expression

  Baseline to 8 weeks

• Change in Growth Factors

  Baseline to 30 days post-treatment

Study Arms (1)

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.

Other: Laboratory Biomarker Analysis; Drug: Nintedanib; Other: Pharmacological Study; Other: Quality-of-Life Assessment

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nintedanib)

Nintedanib DRUG

Given PO

Also known as: BIBF 1120, BIBF-1120, Intedanib, Multitargeted Tyrosine Kinase Inhibitor BIBF 1120, tyrosine kinase inhibitor BIBF 1120, Vargatef

Treatment (nintedanib)

Pharmacological Study OTHER

Correlative studies

Treatment (nintedanib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (nintedanib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Carcinoid Tumor; Neuroendocrine Tumors

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Katy Wang
• Organization: Roswell Park Comprehensive Cancer Center

Chong.Wang@Roswellpark.org

716-845-1300

Study Officials

• Renuka Iyer

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2015
• First Posted: March 26, 2015
• Study Start: May 15, 2015
• Primary Completion: September 1, 2019
• Study Completion: August 31, 2022
• Last Updated: December 26, 2023
• Results First Posted: June 28, 2022

Record last verified: 2023-12

Locations

US (2)