Regorafenib Plus Gemcitabine in Metastatic Pancreatic Cancer

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02383433
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 22.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well regorafenib and gemcitabine hydrochloride work as second-line therapy (treatment given when initial treatment doesn't work) in treating patients with pancreatic cancer that has spread to other parts of the body. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving regorafenib together with gemcitabine hydrochloride may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Adenocarcinoma	Drug: Regorafenib; Drug: Gemcitabine Hydrochloride	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the efficacy (progression-free survival) of regorafenib and gemcitabine (gemcitabine hydrochloride) in previously treated patients with metastatic pancreatic cancer.

SECONDARY OBJECTIVES:

1. To assess the safety of regorafenib in combination with gemcitabine. II. To assess response rate (RR). III. To assess overall survival (OS).

OUTLINE:

Patients receive regorafenib orally (PO) once daily (QD) on days 1-21 and gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up to 30 days and then every 3 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Second-Line Therapy With Regorafenib Plus Gemcitabine in Metastatic Pancreatic Cancer
• Actual Study Start Date: Jun 14, 2016
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: May 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (regorafenib, gemcitabine hydrochloride) Patients receive regorafenib PO QD on days 1-21 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Regorafenib; Given PO; Other Names: BAY 73-4506 multikinase inhibitor BAY 73-4506 Stivarga ; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdC dFdCyd

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Up to 1 year from enrollment]

   Time-to-event data will be summarized using the Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant)

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan

• Prior Therapies: Patients must have received at least one prior systemic chemotherapy regimen for metastatic pancreatic cancer. They should have experienced disease progression or intolerable toxicity from that regimen.

• Patients who have received prior non-gemcitabine-based systemic chemotherapy for metastatic disease at any time 4 weeks prior to enrollment, or those who are beyond 12 months of exposure to gemcitabine-based chemotherapy regimen are allowed.

• Prior chemotherapy, radiation therapy, concurrent chemoradiation are allowed if used for treatment of non-metastatic disease.

• Any chemotherapy must have been completed 4 weeks prior to enrollment

• Any radiotherapy must have been completed 2 weeks prior to enrollment

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• 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; a signed informed consent form 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)

• 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; (subjects who are therapeutically 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 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)

• Platelet count >= 100000/mm^{3, hemoglobin (Hb) ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1500/mm}3; blood transfusion to meet the inclusion criteria will not be allowed

• 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

• Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 3 months after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate

• Subject must be able to swallow and retain oral medication

Exclusion Criteria:

• Chemotherapy within 4 weeks prior to entering the study, radiotherapy within 2 weeks prior to entering the study or failure to recover from adverse events to grade 1 or less due to agents administered more than 4 weeks earlier

• Use of any other investigational agents

• 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 informed consent

• Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from pancreatic 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 phaeochromocytoma

• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy

• Any infection requiring ongoing intravenous antibiotics for management

• Symptomatic metastatic brain or meningeal tumors; treated and stable, asymptomatic brain metastases, as long as treatment was greater than 4 weeks prior to informed consent, are allowed

• Presence of a non-healing wound, non-healing ulcer, or bone fracture

• Renal failure requiring hemo-or peritoneal dialysis

• Dehydration grade >= 1 NCI-CTCAE v4.0

• Patients with seizure disorder requiring medication

• Persistent proteinuria >= grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample)

• Interstitial lung disease with ongoing signs and symptoms at the time of informed consent

• Pleural effusion or ascites that causes respiratory compromise (>= NCI-CTCAE version 4.0 grade 2 dyspnea)

• History of organ allograft (including corneal transplant)

• Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial

• Any malabsorption condition

• Women who are pregnant or breast-feeding

• Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation

• Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Davendra Sohal, MD, MPH, Case Comprehensive Cancer Center
• Principal Investigator: Jennifer Eads, MD, Case Comprehensive Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 7, 2016

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02383433
• Other Study ID Numbers: CASE5214; NCI-2015-00146; CASE5214; P30CA043703
• First Posted: Mar 9, 2015
• Last Update Posted: Jun 27, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Gemcitabine

Study Results

Participant Flow

Arm/Group Title	Treatment (Regorafenib, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive regorafenib PO QD on days 1-21 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regorafenib: Given PO Gemcitabine Hydrochloride: Given IV
Period Title: Overall Study
STARTED	2
COMPLETED	0
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Regorafenib, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive regorafenib PO QD on days 1-21 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regorafenib: Given PO Gemcitabine Hydrochloride: Given IV
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	2 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Time-to-event data will be summarized using the Kaplan-Meier method.
Time Frame	Up to 1 year from enrollment

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome, study terminated early due to low accrual.

Arm/Group Title	Treatment (Regorafenib, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive regorafenib PO QD on days 1-21 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regorafenib: Given PO Gemcitabine Hydrochloride: Given IV
Measure Participants	0

Adverse Events

Time Frame	Adverse events collected up to 3 months while on treatment.
Arm/Group Title	Treatment (Regorafenib, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive regorafenib PO QD on days 1-21 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regorafenib: Given PO Gemcitabine Hydrochloride: Given IV
All Cause Mortality
	Treatment (Regorafenib, Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Serious Adverse Events
	Treatment (Regorafenib, Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
Colitis	1/2 (50%)	1
Nausea	1/2 (50%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign	1/2 (50%)	1
Vascular disorders
Hepatic Vein Thrombus	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Regorafenib, Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
Abdominal Pain	1/2 (50%)	1
Colitis	1/2 (50%)	1
Intermittent Nausea	1/2 (50%)	1
General disorders
Intermittent Fatigue	1/2 (50%)	1
Infections and infestations
Infections, other : Thrush mouth	1/2 (50%)	1
Sinusitis	1/2 (50%)	1
Investigations
Alkaline phosphatase increased	1/2 (50%)	2
alkaline phosphatase, increased gr1	1/2 (50%)	1
ALT increased	1/2 (50%)	8
ALT increased, gr1	1/2 (50%)	1
Aspartate Aminotransferase Increased	1/2 (50%)	1
AST increased	1/2 (50%)	1
decreased platelets	1/2 (50%)	1
increased ALT	1/2 (50%)	1
Increased creatinine	1/2 (50%)	1
Increased Lipase	1/2 (50%)	1
Leukopenia, gr1	1/2 (50%)	1
Lymphocyte Count decreased	1/2 (50%)	1
neutropenia	1/2 (50%)	1
platelet count decreased	1/2 (50%)	1
Thombocytopenia	1/2 (50%)	1
Thrombocytopenia	1/2 (50%)	1
Thrombocytopenia, gr1	1/2 (50%)	1
Weight Gain	1/2 (50%)	1
Weight Loss	1/2 (50%)	1
White blood cell count decreased	1/2 (50%)	1
Metabolism and nutrition disorders
Anorexia	1/2 (50%)	1
Dehydration	1/2 (50%)	1
Hyperglycemia	1/2 (50%)	2
Hyperglycemia, gr1	1/2 (50%)	1
Hypoalbuminemia	1/2 (50%)	1
Hypokalemia	1/2 (50%)	2
Hyponatremia	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
muscle soreness, R shoulder, gr1	1/2 (50%)	1
Neck Pain	1/2 (50%)	1
Nervous system disorders
Dizziness	1/2 (50%)	1
Headache	1/2 (50%)	2
Sinus Pain	1/2 (50%)	1
Psychiatric disorders
depression	1/2 (50%)	1
Renal and urinary disorders
Proteinuria	1/2 (50%)	2
Skin and subcutaneous tissue disorders
Petechial Rash, gr1	1/2 (50%)	1
pruritis	1/2 (50%)	1
pruritis, gr1	1/2 (50%)	1
sunburn	1/2 (50%)	1
Vascular disorders
Hepatic Vein Thrombosis	1/2 (50%)	1
hypertension	1/2 (50%)	6
Intermittent Hypertension	1/2 (50%)	1
worsening hypertension, gr2	1/2 (50%)	1

Limitations/Caveats

Data was not collected, study terminated early due to low accrual.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.