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Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors

Primary Purpose

Gastrinoma, Glucagonoma, Insulinoma

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

temozolomide

capecitabine

About this trial

This is an interventional treatment trial for Gastrinoma focused on measuring temozolomide, capecitabine, pancreatic neuroendocrine tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient must have histologically or pathologically confirmed locally unresectable or metastatic low or intermediate grade pancreatic neuroendocrine tumor
Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; baseline measurements and evaluations of all sites of disease must be obtained <= 4 weeks prior to randomization and must be acquired by multiphasic CT or contrast magnetic resonance imaging (MRI)
Date of last documented disease progression must be within 12 months from date of randomization
Prior everolimus and/or sunitinib therapy is allowed, so long as it was discontinued >= 4 weeks prior to randomization
Concurrent somatostatin analogues are allowed provided that patients
- Have been on a stable dose for 8 weeks and
- Have documented disease progression on that dose
Chemoembolization is allowed if ≥ 4 weeks from study entry. There are 2 possible scenarios:
- If patient has hepatic disease only: they need to have progressed in the liver since chemoembolization and have measurable disease by RECIST 1.1 in order to be eligible.
- If patient has hepatic and extrahepatic disease: they will need to have progressed inside OR outside the liver and have measureable disease by RECIST 1.1 in order to be eligible.
Leukocytes >= 3,000/mm^3
Absolute neutrophil count >= 1,500/mm^3
Hemoglobin >= 9 g/dL
Platelets >= 100,000/mm^3
Total bilirubin <= institutional upper limit of normal (ULN) or <= 1.5 X institutional ULN (if the patient has liver metastases)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) <= 3 X institutional ULN or (<= 5 X institutional ULN if the patient has liver metastases)
Serum creatinine <= 1.5 X institutional ULN
Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Patient must have life expectancy >= 12 weeks all females of childbearing potential must have a blood test or urine study within =< 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
Patient must be able to swallow pills
Patient must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol

Exclusion Criteria:

Small cell carcinoma
Prior temozolomide, dacarbazine (DTIC), or capecitabine, or 5-FU (fluorouracil) therapy
Receiving any other investigational agents while on study treatment
Receiving Coumadin while on treatment; other anticoagulants are allowed
Patients with either clinically apparent central nervous system metastases or carcinomatous meningitis are ineligible
Active or uncontrolled infection or serious medical or psychiatric illness
History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine
Absorption issues that would limit the ability to absorb study agents
Patients with a history of the following within 12 months of study entry:
- Arterial thromboembolic events
- Unstable angina
- Myocardial Infarction
Symptomatic peripheral vascular disease
Patients with previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:
- Non-melanoma skin cancer, in situ cervical cancer, or breast cancer in situ OR
- Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years OR
- Prior malignancy cured by non-surgical modalities and patient has been continuously disease free for > 5 years
Pregnant or breast-feeding

Sites / Locations

Kaiser Anaheim Medical Center
Kaiser Permanente-Deer Valley Medical Center
Kaiser Permanente Medical Group - Baldwin Park
Kaiser Foundation Hospital
Alta Bates Summit Medical Center-Herrick Campus
Mills - Peninsula Hospitals
Kaiser Permanente Hospital
Kaiser Permanente, Fremont
Kaiser Permanente
Kaiser Permanente - Harbor City
Kaiser Permanente, Hayward
Southern California Permanente Medical Group
Kaiser Permanente Los Angeles Medical Center
University of Southern California/Norris Cancer Center
Kaiser Permanente-West Los Angeles
Cedars-Sinai Medical Center
Kaiser Permanente-Modesto
Sutter Cancer Research Consortium
Kaiser Permanente-Oakland
University of California Medical Center At Irvine-Orange Campus
Kaiser Permanente - Panorama City
Kaiser Permanente-Redwood City
Kaiser Permanente-Richmond
Kaiser Permanente Medical Center
Kaiser Permanente-Roseville
Kaiser Permanente-South Sacramento
Kaiser Permanente - Sacramento
Kaiser Permanente at San Diego
Kaiser Permanente
Kaiser Permanente-San Francisco
UCSF-Mount Zion
California Pacific Medical Center
Kaiser Permanente-Santa Teresa-San Jose
Kaiser Permanente Health Care
Kaiser Permanente-San Rafael
Kaiser Permanente Medical Center - Santa Clara
Kaiser Permanente-Santa Rosa
Sutter Pacific Medical Foundation
Kaiser Permanente-South San Francisco
Stanford University Hospitals and Clinics
Kaiser Permanente-Stockton
Kaiser Permanente Medical Center-Vacaville
Kaiser Permanente-Vallejo
Sutter Solano Medical Center
Kaiser Permanente-Walnut Creek
Kaiser Permanente
Saint Francis Hospital and Medical Center
Middlesex Hospital
Beebe Medical Center
Christiana Gynecologic Oncology LLC
Delaware Clinical and Laboratory Physicians PA
Helen F Graham Cancer Center
Medical Oncology Hematology Consultants PA
Regional Hematology and Oncology PA
Christiana Care Health System-Christiana Hospital
Beebe Health Campus
Nanticoke Memorial Hospital
Christiana Care Health System-Wilmington Hospital
Edna Williams Cancer Center at the Baptist Cancer Institute
University of Miami Miller School of Medicine-Sylvester Cancer Center
Florida Hospital
H. Lee Moffitt Cancer Center and Research Institute
Oncare Hawaii Inc-Pali Momi
Pali Momi Medical Center
Oncare Hawaii Inc-POB II
Queen's Medical Center
Straub Clinic and Hospital
University of Hawaii
OnCare Hawaii-Liliha
Oncare Hawaii Inc-Kuakini
Kaiser Permanente Moanalua Medical Center
Castle Medical Center
Wilcox Memorial Hospital and Kauai Medical Clinic
Saint Alphonsus Regional Medical Center
Illinois CancerCare-Bloomington
Saint Joseph Medical Center
Illinois CancerCare-Canton
Memorial Hospital of Carbondale
Illinois CancerCare-Carthage
Centralia Oncology Clinic
Northwestern University
University of Illinois
Cancer Care Center of Decatur
Decatur Memorial Hospital
Crossroads Cancer Center
Illinois CancerCare-Eureka
Illinois CancerCare Galesburg
Illinois CancerCare-Galesburg Cottage Plaza Office
Hematology Oncology Associates of Illinois-Highland Park
Hinsdale Hematology Oncology Associates Incorporated
Presence Saint Mary's Hospital
Illinois CancerCare-Kewanee Clinic
North Shore Hematology Oncology
Illinois CancerCare-Macomb
Loyola University Medical Center
Garneau, Stewart C MD (UIA Investigator)
Porubcin, Michael MD (UIA Investigator)
Spector, David MD (UIA Investigator)
Trinity Medical Center
Illinois CancerCare-Monmouth
Good Samaritan Regional Health Center
Illinois Cancer Specialists-Niles
Community Cancer Center Foundation
Illinois CancerCare-Ottawa Clinic
Ottawa Regional Hospital and Healthcare Center
Pekin Cancer Treatment Center
Illinois CancerCare-Pekin
Methodist Medical Center of Illinois
Proctor Hospital
Illinois CancerCare-Peoria
Illinois Oncology Research Association CCOP
OSF Saint Francis Medical Center
Illinois CancerCare-Peru
Illinois CancerCare-Princeton
SwedishAmerican Regional Cancer Center/ACT
Hematology Oncology Associates of Illinois - Skokie
Memorial Medical Center
Franciscan Saint Francis Health-Indianapolis
Reid Hospital and Health Care Services
Mary Greeley Medical Center
McFarland Clinic PC-William R Bliss Cancer Center
Constantinou, Costas L MD (UIA Investigator)
McFarland Clinic PC-Boone
Medical Oncology and Hematology Associates-West Des Moines
Mercy Cancer Center-West Lakes
Iowa Methodist Medical Center
Iowa Oncology Research Association CCOP
Medical Oncology and Hematology Associates-Des Moines
Medical Oncology and Hematology Associates-Laurel
Mercy Medical Center - Des Moines
Iowa Lutheran Hospital
McFarland Clinic PC-Jefferson
McFarland Clinic PC-Marshalltown
Siouxland Hematology Oncology Associates
Mercy Medical Center-Sioux City
Saint Luke's Regional Medical Center
Methodist West Hospital
Mercy Medical Center-West Lakes
Cancer Center of Kansas - Chanute
Cancer Center of Kansas - Dodge City
Cancer Center of Kansas - El Dorado
Cancer Center of Kansas - Fort Scott
Cancer Center of Kansas-Independence
Cancer Center of Kansas-Kingman
Lawrence Memorial Hospital
Cancer Center of Kansas-Liberal
Cancer Center of Kansas-Manhattan
Cancer Center of Kansas - McPherson
Cancer Center of Kansas - Newton
Cancer Center of Kansas - Parsons
Cancer Center of Kansas - Pratt
Cancer Center of Kansas - Salina
Cancer Center of Kansas - Wellington
Associates In Womens Health
Cancer Center of Kansas-Wichita Medical Arts Tower
Cancer Center of Kansas - Main Office
Via Christi Regional Medical Center
Wichita CCOP
Cancer Center of Kansas - Winfield
Oncology Hematology Care Incorporated
Ochsner Health Center-Summa
Ochsner Medical Center Jefferson
Boston Medical Center
Lahey Hospital and Medical Center
Bixby Medical Center
Hickman Cancer Center
Saint Joseph Mercy Hospital
Michigan Cancer Research Consortium Community Clinical Oncology Program
University of Michigan University Hospital
Oakwood Hospital
Saint John Hospital and Medical Center
Hurley Medical Center
Genesys Hurley Cancer Institute
Allegiance Health
Borgess Medical Center
Bronson Methodist Hospital
West Michigan Cancer Center
Sparrow Hospital
Saint Mary Mercy Hospital
Community Cancer Center of Monroe
Mercy Memorial Hospital
Saint Joseph Mercy Oakland
Saint Joseph Mercy Port Huron
Saint Mary's of Michigan
Saint John Macomb-Oakland Hospital
Fairview Ridges Hospital
Mercy Hospital
Fairview-Southdale Hospital
Unity Hospital
Hutchinson Area Health Care
Minnesota Oncology Hematology PA-Maplewood
Saint John's Hospital - Healtheast
Abbott-Northwestern Hospital
Hennepin County Medical Center
New Ulm Medical Center
North Memorial Medical Health Center
Metro-Minnesota CCOP
Park Nicollet Clinic - Saint Louis Park
Regions Hospital
United Hospital
Saint Francis Regional Medical Center
Lakeview Hospital
Ridgeview Medical Center
Rice Memorial Hospital
Minnesota Oncology and Hematology PA-Woodbury
Central Care Cancer Center-Carrie J Babb Cancer Center
CoxHealth Cancer Center
Saint Francis Medical Center
Southeast Cancer Center
Capital Region Medical Center-Goldschmidt Cancer Center
Phelps County Regional Medical Center
Saint John's Clinic-Rolla-Cancer and Hematology
Saint Louis Cancer and Breast Institute-South City
Missouri Baptist Medical Center
Saint John's Mercy Medical Center
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
Mercy Hospital Springfield
CoxHealth South Hospital
Nebraska Methodist Hospital
Nevada Cancer Research Foundation CCOP
Cooper Hospital University Medical Center
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
Virtua West Jersey Hospital Voorhees
New York Oncology Hematology PC - Albany
New York Oncology Hematology PC -Albany Medical Center
New York Oncology Hematology PC - Amsterdam
Montefiore Medical Center-Weiler Division
Montefiore Medical Center
New York Oncology Hematology PC-Hudson
New York Oncology Hematology PC - Latham
New York Oncology Hematology PC - Rexford
University of Rochester
New York Oncology Hematology PC - Troy
Kinston Medical Specialists PA
Iredell Memorial Hospital
Akron General Medical Center
Cleveland Clinic Cancer Center Beachwood
Strecker Cancer Center-Belpre
Toledo Clinic Cancer Centers-Bowling Green
Adena Regional Medical Center
Oncology and Hematology Care Incorporated
Oncology Hematology Care Inc - Anderson
Oncology Hematology Care Inc - Kenwood
Oncology and Hematology Care Inc - Blue Ash
Oncology Hematology Care Inc - Western Hills
University of Cincinnati
Case Western Reserve University
Cleveland Clinic Foundation
Ohio State University Medical Center
Columbus Oncology and Hematology Associates Inc
Riverside Methodist Hospital
Columbus CCOP
Grant Medical Center
The Mark H Zangmeister Center
Mount Carmel Health Center West
Doctors Hospital
Grandview Hospital
Good Samaritan Hospital - Dayton
Miami Valley Hospital
Samaritan North Health Center
Dayton CCOP
Delaware Health Center-Grady Cancer Center
Delaware Radiation Oncology
Grady Memorial Hospital
Hematology Oncology Center Incorporated
Mercy Cancer Center-Elyria
Oncology Hematology Care Inc
Blanchard Valley Hospital
Atrium Medical Center-Middletown Regional Hospital
Wayne Hospital
Cleveland Clinic Cancer Center Independence
Kettering Medical Center
Fairfield Medical Center
Lancaster Radiation Oncology
Saint Rita's Medical Center
Lima Memorial Hospital
Marietta Memorial Hospital
Toledo Clinic Cancer Centers-Maumee
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
Hillcrest Hospital Cancer Center
Knox Community Hospital
Licking Memorial Hospital
Newark Radiation Oncology
Saint Charles Hospital
Toledo Clinic Cancer Centers-Oregon
Southern Ohio Medical Center
North Coast Cancer Care
Springfield Regional Medical Center
Cleveland Clinic Cancer Center-Strongsville
Flower Hospital
Mercy Hospital of Tiffin
The Toledo Hospital/Toledo Children's Hospital
Saint Vincent Mercy Medical Center
University of Toledo
Toledo Community Hospital Oncology Program CCOP
Mercy Saint Anne Hospital
Toledo Clinic Cancer Centers-Toledo
Upper Valley Medical Center
Fulton County Health Center
Saint Ann's Hospital
Greene Memorial Hospital
Genesis HealthCare System
University of Oklahoma Health Sciences Center
Tulsa Cancer Institute
Geisinger Medical Center
Geisinger Medical Center-Cancer Center Hazleton
Penn State Milton S Hershey Medical Center
Geisinger Medical Oncology at Evangelical Community Hospital
Thomas Jefferson University Hospital
Fox Chase Cancer Center
Geisinger Medical Oncology-Pottsville
Geisinger Medical Group
Reading Hospital
Geisinger Wyoming Valley
Greenville Health System Cancer Institute-Butternut
Greenville Health System Cancer Institute/Greenville CCOP
Greenville Health System Cancer Institute-Greer
Vanderbilt Cancer Center
Fredericksburg Oncology Inc
Gundersen Lutheran
University of Wisconsin Hospital and Clinics
Froedtert and the Medical College of Wisconsin
Cancer Center of Western Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm A (temozolomide)

Arm B (temozolomide and capecitabine)

Arm Description

Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Progression-free Survival

Progression-free survival (PFS) is defined as the time from randomization to progression or death without evidence of progression. Progression was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier method was used to estimate PFS.

Secondary Outcome Measures

Proportion of Patients With Response

Overall Survival

Overall survival is defined as time from randomization to death or date last known alive.

Association Between Methyl Guanine Methyltransferase (MGMT) Status by Immunohistochemistry (IHC) and Response

Response was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and defined as either complete response (CR) or partial response (PR). CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. MGMT status was determined by IHC using paraffin-embedded sections of 4µm. A score (H-score) was generated based on the findings and scoring was performed by two pathologists. This H-score ranges from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor). The highest score was used if there was disagreement. H-scores were grouped into 3 standard categories for MGMT status: Category 1 - <=50 Category 2 - 51-100 Category 3 - >100

Association Between Methyl Guanine Methyltransferase (MGMT) Status by Promoter Methylation and Response

Response was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and defined as either complete response (CR) or partial response (PR). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. MGMT status is determined by promoter methylation, a clinically validated methylation-specific polymerase chain reaction (PCR) analysis. A tumor sample is considered positive for MGMT promoter methylation if an 80bp band is detected in the methylated PCR reaction. It would be considered MGMT negative if an 80bp band is not detected in the methylated PCR reaction.

Full Information

NCT ID

NCT01824875

First Posted

April 2, 2013

Last Updated

June 14, 2023

Sponsor

ECOG-ACRIN Cancer Research Group

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01824875

Brief Title

Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors

Official Title

A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 8, 2013 (Actual)

Primary Completion Date

May 26, 2021 (Actual)

Study Completion Date

July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ECOG-ACRIN Cancer Research Group

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This randomized phase II trial studies how well giving temozolomide with or without capecitabine works in treating patients with advanced pancreatic neuroendocrine tumors. Drugs used in chemotherapy, such as temozolomide and capecitabine, 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. It is not yet known whether temozolomide is more effective with or without capecitabine in treating patients with advanced pancreatic neuroendocrine tumors.

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate progression-free survival (PFS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors. SECONDARY OBJECTIVES: I. To evaluate response rates (RR) associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors. II. To evaluate overall survival (OS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors. III. To evaluate the toxicity associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors. IV. To evaluate the usefulness of methyl guanine methyltransferase (MGMT) status (by immunohistochemistry [IHC] and promoter methylation) for predicting response in pancreatic neuroendocrine tumor patients treated with either temozolomide or temozolomide and capecitabine. V. To bank radiology images for evaluation of quality, reproducibility, and compliance with computed tomography (CT) methodology. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive capecitabine PO twice daily (BID) on days 1-14 and temozolomide PO QD on days 10-14. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastrinoma, Glucagonoma, Insulinoma, Islet Cell Carcinoma, Pancreatic Polypeptide Tumor, Recurrent Islet Cell Carcinoma, Somatostatinoma

Keywords

temozolomide, capecitabine, pancreatic neuroendocrine tumor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

144 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A (temozolomide)

Arm Type

Experimental

Arm Description

Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Arm Title

Arm B (temozolomide and capecitabine)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

temozolomide

Other Intervention Name(s)

Temodar

Intervention Description

Given PO

Intervention Type

Drug

Intervention Name(s)

capecitabine

Other Intervention Name(s)

Xeloda

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Progression-free Survival

Description

Time Frame