Clinical trial NCT02080260: A Study of Regorafenib in Advanced Pancreatic Cancer Patients
Official title: A Pilot Study Testing Single-Agent Regorafenib in Advanced Previously-Treated Adenocarcinoma of the Pancreas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2014-03-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study tests regorafenib as a single agent in the treatment of metastatic pancreatic cancer patients who have progressed after prior chemotherapy with gemcitabine. The prognosis for these patients is particularly grim, no other standard treatment options exist, and novel approaches are desperately needed.

Detailed description: This is a single arm, single stage Phase II study designed to evaluate progression free survival (PFS) in patients with metastatic pancreatic cancer who have failed at least one prior line of therapy and treatment with gemcitabine. This study is open at the Levine Cancer Institute (LCI). A total of 32 patients will be enrolled over a two years. Following informed consent and eligibility check, all patients will start oral regorafenib therapy (120 mg daily for 3 weeks on / 1 week off; 28 day cycle) with a built-in dose escalation to 160mg after the first cycle as tolerated, and will continue therapy until progression or patient withdrawal. Patients will undergo radiological staging after the first two cycles of regorafenib therapy. Patients with progressive disease will be removed from the study. Patients who have at least stable disease will continue regorafenib therapy, at the Investigator's discretion, and will be radiologically restaged bimonthly.

Eligibility criteria: Inclusion Criteria:

* Adenocarcinoma of the exocrine pancreas with metastatic disease.
* The site of the primary tumor confirmed to have been within the pancreas.
* Progression on at least one prior line of chemotherapy for locally-advanced or metastatic pancreatic cancer.
* Progression while on treatment with a gemcitabine regimen for advanced pancreatic cancer, or within 12 months of treatment with gemcitabine as part of adjuvant therapy.
* Measurable disease on axial imaging.
* Age greater than or equal to 18 years.
* Life expectancy of at least 8 weeks.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2. Enrollment of patients with PS = 2 will be capped at 7 patients.
* Subjects must be able to understand and be willing to sign the written informed consent form.
* Acute toxic effects except alopecia of any prior treatment must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade 1 or less.
* Adequate bone marrow, renal, and liver function.
* Warfarin or heparin will be allowed provided that there is no prior evidence of underlying coagulation abnormality.
* Women of childbearing potential must have a negative 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 (men and women) of childbearing potential must agree to use adequate contraception
* Patient must be able to swallow and retain oral medication.

Exclusion Criteria:

* Previous assignment to treatment during this study.
* Uncontrolled hypertension.
* Active clinically significant cardiac disease.
* Cerebrovascular arterial event within 6 months.
* Evidence or history of bleeding diathesis or coagulopathy.
* Any bleeding event greater than or equal to NCI CTCAE Grade 3 within 4 weeks.
* New venous thrombotic or embolic events, such as deep vein thrombosis or pulmonary embolism within 3 months.
* Previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Patients surviving a cancer that was curatively treated and without evidence of disease for more than 3 years are allowed.
* Patients with pheochromocytoma.
* Known history of HIV infection or current chronic or active hepatitis B or C, requiring antiviral medication.
* Ongoing infection greater than or equal to Grade 2 NCI-CTCAE v4.0.
* Symptomatic metastatic brain or meningeal tumors.
* Presence of a non-healing wound, non-healing ulcer, or bone fracture.
* Renal failure requiring dialysis.
* Dehydration Grade greater than or equal to 1 NCI-CTCAE v4.0.
* Patients with seizure disorder requiring medication.
* Persistent proteinuria greater than or equal to Grade 3 NCI-CTCAE v4.0.
* Symptomatic interstitial lung disease.
* Pleural effusion or ascites that cause respiratory compromise.
* History of organ allograft except corneal transplant.
* Known or suspected allergy or hypersensitivity to the study drugs.
* Any severe, uncontrolled malabsorption condition.
* Women who are pregnant or breast-feeding.
* Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study.
* Concurrent anti-cancer therapy other than study treatment (regorafenib).
* Prior use of regorafenib.
* Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 4 weeks.
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days.
* Prior radiation therapy or hepatic arterial therapy is permitted if more than 4 weeks have passed since completion and measurable disease outside of the treated area is present, or if progression since treatment has occurred.
* Use of St. John's Wort.

Primary outcomes:
measure: Number of Patients Progression Free and Surviving at 16 Weeks as a Percent of All Enrolled Subjects
timeFrame: 16 weeks after enrollment
Secondary outcomes:
measure: Progression Free Survival
timeFrame: From date of treatment start to date of progression or death, or censored as described above; assessed for approximately 3 years.
measure: Overall Survival
timeFrame: From date of treatment start to date of death, or censored as described above; assessed for approximately 3 years.
measure: Overall Response
timeFrame: From enrollment to best response while on regorafenib; Subjects remained on treatment until disease progression or death or discontinuation from study or at least 28 days after last dose (subjects were on treatment for an average of 6 weeks)
measure: Disease Control
timeFrame: From enrollment to best response while on regorafenib; Subjects remained on treatment until disease progression or death or discontinuation from study or at least 28 days after last dose (subjects were on treatment for an average of 6 weeks)
Other outcomes:
Locations:
city: Albemarle
country: United States
facility: Levine Cancer Institute-Albemarle
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute-South Tryon
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute - Pineville
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute - Southpark
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute - Mallard Creek
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute - University
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute - Ballantyne
state: North Carolina
city: Concord
country: United States
facility: Levine Cancer Institute - Concord
state: North Carolina
city: Monroe
country: United States
facility: Levine Cancer Institute-Monroe
state: North Carolina
city: Shelby
country: United States
facility: Levine Cancer Institute - Cleveland
state: North Carolina
city: Charleston
country: United States
facility: Low Country Hematology Oncology
state: South Carolina
Study officials:
affiliation: Atrium Health Levine Cancer Institute
name: John S Salmon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Atrium Health Levine Cancer Institute
name: Edward Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: