Regorafenib in Reducing Recurrence in Patients With Non-metastatic Rectal Cancer Who Have Completed Curative-Intent Treatment

NCT02287727 | Withdrawn Phase 2 DMC

• 5 other identifiers: I 246813NCI-2014-02202ONC-2013-036BAY ONC-3012-036P30CA016056
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well regorafenib works in reducing the return of disease in patients with rectal cancer that has not spread to another place in the body who have completed curative-intent treatment. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Regorafenib may also help keep cancer from coming back after it has disappeared following the initial therapy.

Conditions

Rectal Adenocarcinoma; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Disease free survival (DFS)

  The DFS will be summarized using the standard Kaplan-Meier methods. The 3-year DFS rate will be estimated by a 95% confidence interval, obtained using the method proposed by Breslow and Day, using the intent-to-treat approach.

  3 years

Secondary Outcomes (5)

• Biomarkers associated with anti-cancer effects of regorafenib maintenance therapy

  Up to 5 years

• Distant recurrence

  3 years

• Frequency of toxicity, graded according to National Cancer Institute CTCAE version 4.0

  Up to 30 days following last dose of study drug

• Local recurrence

  3 years

• Overall survival

  3 years

Study Arms (1)

Treatment (regorafenib)

EXPERIMENTAL

Patients receive regorafenib PO QD on days 1-21. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Regorafenib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (regorafenib)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Stivarga

Treatment (regorafenib)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the rectum that was clinically staged T3, T4 or node-positive (defined as \>= N1 per American Joint Committee on Cancer \[AJCC\] 7th edition) that was treated with the following treatment with curative intent:
• Curative surgical resection
• Pre- or post-operative chemoradiation; and at least 3 months of adjuvant systemic chemotherapy (equivalent to 6 cycles of leucovorin calcium, fluorouracil, and oxaliplatin \[FOLFOX\] or infusional fluorouracil \[5FU\])
• No evidence of cancer within 28 days prior to start of study treatment; this should be determined by imaging of the chest, abdomen and pelvis by computed tomography (CT) and/or magnetic resonance imaging (MRI); staging of the chest using chest x-ray in lieu of CT and/or MRI should not be used for this purpose
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• Consent to allowing his/her archival tumor tissues to be requested and analyzed; however, the non-availability or inadequate amount samples for analysis will not exclude the patient
• Total bilirubin =\< 1.5 x the upper limits of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) =\< 2.5 x ULN
• Alkaline phosphatase limit =\< 2.5 x ULN
• Lipase =\< 1.5 x the ULN
• Serum creatinine =\< 1.5 times the ULN
• International normalized ratio (INR) of prothrombin time (PT; PT-INR) and activated partial thromboplastin time (aPTT) =\< 1.5: subjects who are prophylactically 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 per medical history; close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
• Patients of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and, until at least 3 months after the last dose of the study drug; 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
• Patient is willing and able to take oral medications and to comply with scheduled visits, treatment plan, and study related procedures

You may not qualify if:

• Evidence of recurrence of rectal cancer prior to the start of study treatment
• Any previously untreated or concurrent cancer that is distinct in primary site or histology from rectal 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 starting study drug 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)
• Anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) within 4 weeks prior to entering the study (signing of consent form) or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients on hormonal or bisphosphonate treatment for non-cancer related conditions are eligible
• Inability to start study treatment within 12 weeks following the completion of curative intent therapy for rectal adenocarcinoma
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication; minor procedures such as diagnostic laparoscopy, percutaneous biopsy and paracentesis within 14 days before start of study medication
• Patients who have not recovered from the surgical resection of rectal cancer such as wound dehiscence, non-healing wound, wound infection and fistula
• Prior use of regorafenib
• Gastrointestinal conditions that may significantly affect the absorption of regorafenib
• Uncontrolled hypertension (systolic pressure \> 140 mmHg or diastolic pressure \> 90 mmHg on repeated measurement) despite optimal medical management
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding event \>= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 within 4 weeks prior to start of study medication
• Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 3 months prior to the initiation of study treatment
• Patients with phaeochromocytoma
• 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 \> CTCAE grade 2

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University of Rochester Medical Center - Wilmont Cancer Institute

Rocherster, New York, 14642, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Patrick Boland

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

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: November 6, 2014
• First Posted: November 11, 2014
• Study Start: March 1, 2015
• Primary Completion: October 1, 2016
• Last Updated: October 12, 2016

Record last verified: 2016-10

Locations

US (3)