Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

NCT02259725 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 0S-14-3NCI-2014-01996HS-14-00583P30CA014089
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 5

Brief Summary

This phase II trial studies regorafenib in treating patients with neuroendocrine tumors that have spread from the primary site (place where it started) to other places in the body. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

Outcome Measures

Primary Outcomes (1)

• PFS

  Two parallel Simon's 2-stage phase II trials will be conducted to evaluate the efficacy of regorafenib in patients with advanced carcinoid (cohort A) or pancreatic islet cell tumors (cohort B). Will be summarized as a proportion of patients who are alive and progression-free among all patients in the primary data analysis set. The 95% confidence intervals (CIs) will be calculated using the Wilson method. Will be analyzed using Kaplan-Meier (KM) curves. The median PFS and 95% CIs will be calculated. The probability of 6-month PFS will be estimated from the KM curve too.

  Time from start of treatment to time of progression or death on study whichever comes first, assessed at 6 months

Secondary Outcomes (3)

• Tumor Response Rate, Evaluated Using the New International Criteria Proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee

  Up to 4 years

• Overall Survival

  From start of treatment until death due to any cause, assessed up to 4 years

• Incidence of Adverse Events, Assessed According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  Up to 4 years

Other Outcomes (1)

• Biomarkers Such as Messenger Ribonucleic Acid (mRNA) Levels or Germline Variations of Genes Related to Angiogenesis

  Up to 4 years

Study Arms (1)

Treatment (regorafenib)

EXPERIMENTAL

Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: regorafenib; Other: laboratory biomarker analysis

Interventions

regorafenib DRUG

Given PO

Also known as: BAY 73-4506, multikinase inhibitor BAY 73-4506, Stivarga

Treatment (regorafenib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (regorafenib)

Eligibility Criteria

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

You may qualify if:

• Advanced metastatic, progressing carcinoid or pancreatic islet cell cancers
• No prior targeted treatment (tx) or anti-angiogenic therapy; patients may have received one line of prior therapy with octreotide, locoregional therapy; continuation of concurrent octreotide is allowed; patients will be maintained on octreotide (sandostatin) for the duration of their treatment
• Life expectancy of at least 12 weeks (3 months)
• Subjects must be able to understand and be willing to sign the written informed consent form (ICF); a signed ICF must be appropriately obtained prior to the conduct of any trial-specific procedure
• All acute toxic effects of any prior treatment have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v)4.0 grade 1 or less at the time of signing the informed consent form (ICF); exceptions to this include alopecia
• Total bilirubin =\< 1.5 x the upper limits of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
• Alkaline phosphastase limit =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
• Lipase =\< 1.5 x the ULN
• Amylase =\< 1.5 x the ULN
• Serum creatinine =\< 1.5 x the ULN
• International normalized ratio (INR)/ partial thromboplastin time (PTT) \< 1.5 x ULN; (subjects who are treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring \[day 5 of cycle 1 and day 1 of each cycle\] is mandatory) will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care)
• Platelet count \>= 100,000 /mm\^3
• Hemoglobin (Hb) \>= 9 g/dL
• Glomerular filtration rate (GFR) \>= 30 ml/min/1.73 m\^2 according to the Modified Diet in Renal Disease (MDRD) abbreviated formula

You may not qualify if:

• Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
• Uncontrolled hypertension (systolic pressure \> 140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI-CTCAE v4.0\] on repeated measurement) despite optimal medical management
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association (NYHA) \> class II
• Active coronary artery disease
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding event \>= NCI-CTCAE grade 3 within 4 weeks prior to start of study medication
• Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment
• Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from carcinoid or pancreatic islet cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed; all cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form)
• Patients with pheochromocytoma
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
• Ongoing infection \> grade 2 NCI-CTCAE v4.0
• Presence of a non-healing wound, non-healing ulcer, or bone fracture

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

USC Norris Oncology Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Carcinoma, Islet Cell; Somatostatinoma

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenoma, Islet Cell; Adenoma; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal

Results Point of Contact

• Title: Victoria Soto
• Organization: USC / Norris Comprehensive Cancer Center

soto_v@med.usc.edu

3238653000

Study Officials

• Syma Iqbal, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: October 3, 2014
• First Posted: October 8, 2014
• Study Start: August 16, 2016
• Primary Completion: August 20, 2020
• Study Completion: August 20, 2020
• Last Updated: December 15, 2021
• Results First Posted: December 15, 2021

Record last verified: 2021-11

Locations

US (5)