Regorafenib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction Who Have Completed Chemoradiation Therapy and Surgery

NCT02234180 | Terminated Phase 2 Results DMC

• 4 other identifiers: RU021212INCI-2015-01699NCI-2014-01962P30CA015083
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 10

Brief Summary

This randomized phase II trial studies how well regorafenib works in treating patients with cancer of the esophagus or gastroesophageal junction that has spread from where it started to nearby tissue or lymph nodes and have completed chemoradiation therapy and surgery. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Adenocarcinoma of the Gastroesophageal Junction; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival (DFS)

  Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause. The distribution of DFS will be estimated using the Kaplan Meier method.

  Time from randomization to the first of either disease recurrence or death from any cause, assessed up to 1 year and 10 months

Secondary Outcomes (2)

• Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)

  Up to 1 year and 10 months

• Overall Survival (OS)

  Time from randomization to death due to any cause, assessed up to 1 year and 10 months

Study Arms (2)

Arm I (regorafenib)

EXPERIMENTAL

Within 6-12 weeks after surgery, patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Drug: Regorafenib

Arm II (placebo)

PLACEBO COMPARATOR

Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Other: Placebo

Interventions

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Stivarga

Arm I (regorafenib)

Eligibility Criteria

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

You may qualify if:

• Histological confirmation of node positive (any T stage N1-3) proximal esophageal, distal esophagus or gastroesophageal (GE) junction adenocarcinoma (Siewert I, II, or III) after completing preoperative chemoradiation and surgery; supporting pathology report sufficient for registration; available tumor tissue from endoscopic biopsies prior to preoperative chemotherapy (chemo)/radiation therapy (RT), and tumor from surgical specimens will be submitted to Academic and Community Cancer Research United (ACCRU), but not be required prior registration; Note: if tissue is depleted, patient will still be eligible after discussion with the physician
• Imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) =\< 28 days of study registration negative for disease recurrence
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelet count \>= 100,000/mm\^3
• 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 phosphatase limit =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
• Lipase =\< 1.5 x the ULN
• Serum creatinine =\< 1.5 x the ULN
• International normalized ratio (INR)/partial thromboplastin time (PTT) =\< 1.5 x ULN; Note-subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that their medication dose and INR/PTT are stable; close monitoring (day 1 of each cycle) is mandatory; if either of these values is above the therapeutic range, the doses should be modified and the assessments should be repeated weekly until they are stable
• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Provide informed written consent
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
• Able to swallow and retain oral medications and begin therapy within 6 to 12 weeks post-surgery

You may not qualify if:

• Presence of metastatic or recurrent disease
• R1 or R2 resection
• Patients who have not recovered from serious adverse events (as determined by treating doctor of medicine \[MD\]) related to surgery
• Uncontrolled hypertension (systolic pressure \> 140 mm Hg or diastolic pressure \> 90 mm Hg on repeated measurement) despite optimal medical management per physician discretion
• 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 \< 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 \>= National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 grade 3 =\< 4 weeks prior to registration
• Prior cancers \< 3 years, with the exception of in-situ cervical cancer, low grade prostate cancer and basal or squamous cell skin cancers
• Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism =\< 6 months prior to registration
• Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); use of strong or moderate inhibitors are prohibited =\< 7 days to registration
• Receiving any medications or substances that are inducers of CYP3A4; use of inducers are prohibited =\< 7 days prior to registration

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Cancer Center of Kansas - Wichita

Wichita, Kansas, 67214, United States

Location

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Toledo Clinic Cancer Centers-Toledo

Toledo, Ohio, 43623, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

regorafenib

Results Point of Contact

• Title: Yelena Y. Janjigian MD
• Organization: Memorial Sloan-Kettering Cancer Center

janjigiy@mskcc.org

646-888-4186

Study Officials

• Yelena Janjigian

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2014
• First Posted: September 9, 2014
• Study Start: September 1, 2014
• Primary Completion: June 8, 2016
• Study Completion: June 8, 2016
• Last Updated: October 17, 2018
• Results First Posted: October 17, 2018

Record last verified: 2018-10

Locations

US (10)