Testing The Use Of Chemotherapy After Surgery For High-Risk Pancreatic Neuroendocrine Tumors

Study Overview

Testing the Use of Chemotherapy After Surgery for High-Risk Pancreatic Neuroendocrine Tumors

This phase II trial studies the effect of capecitabine and temozolomide after surgery in treating patients with high-risk well-differentiated pancreatic neuroendocrine tumors. Chemotherapy drugs, such as capecitabine and temozolomide, 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 capecitabine and temozolomide after surgery could prevent or delay the return of cancer in patients with high-risk well-differentiated pancreatic neuroendocrine tumors.

PRIMARY OBJECTIVE: I. To evaluate recurrence-free survival (RFS) in participants with resected pancreatic neuroendocrine tumors (pNETs) randomized to treatment with capecitabine + temozolomide (CAPTEM) compared to observation only. SECONDARY OBJECTIVES: I. To evaluate overall survival (OS) in participants randomized to treatment with CAPTEM compared to observation only. II. To evaluate the safety and tolerability of CAPTEM compared to observation only. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14 and temozolomide PO once daily (QD) on days 10-14. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo surveillance with no active treatment. After completion of study treatment, patients are followed up every 6 months for 3 years and then annually until 5 years from randomization.

Metastatic Malignant Neoplasm in the Liver
Pancreatic Neuroendocrine Tumor
Stage I Pancreatic Neuroendocrine Tumor AJCC v8
Stage II Pancreatic Neuroendocrine Tumor AJCC v8
Stage III Pancreatic Neuroendocrine Tumor AJCC v8

DRUG: Capecitabine
DRUG: Temozolomide

S2104
NCI-2021-06619 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
S2104 (OTHER Identifier) (OTHER: SWOG)
S2104 (OTHER Identifier) (OTHER: CTEP)
U10CA180888 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-09-02	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-03
First Submitted that Met QC Criteria 2021-09-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-06
First Posted (ACTUAL) 2021-09-10	Results First Posted N/A	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm I (capecitabine, temozolomide) Patients receive capecitabine PO BID on days 1-14 and temozolomide PO once QD on days 10-14. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.	DRUG: Capecitabine Given PO DRUG: Temozolomide Given PO
NO_INTERVENTION: Arm II (surveillance) Patients undergo surveillance with no active treatment.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm I (capecitabine, temozolomide)

Patients receive capecitabine PO BID on days 1-14 and temozolomide PO once QD on days 10-14. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

DRUG: Capecitabine

Given PO

DRUG: Temozolomide

Given PO

NO_INTERVENTION: Arm II (surveillance)

Patients undergo surveillance with no active treatment.

Primary Outcome Measures	Measure Description	Time Frame
Recurrence-free survival (RFS)	Distribution of RFS in each arm will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.	From date of randomization to progression/recurrence or death from any cause, assessed up to 5 years

Secondary Outcome Measures	Measure Description	Time Frame
Overall survival (OS)	Distribution of OS in each arm will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.	From date of registration to date of death due to any cause, assessed up to 5 years
Incidence of adverse events	Evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.	Up to 30 days after completion of treatment

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Participants must have a histologic diagnosis of well-differentiated pancreatic neuroendocrine tumor (pNET) that was resected between 14 and 90 days prior to registration. Participants must have a scan within 90 days prior to registration without evidence of metastatic disease. Acceptable scans are multiphase computed tomography (CT) abdomen, magnetic resonance imaging (MRI) with intravenous (IV) contrast of the abdomen, or positron emission tomography (PET)-CT DOTATATE imaging if the DOTATATE PET-CT included IV iodine contrast for the CT portion of the exam
Resection must have been an R0 or R1 per treating investigator's assessment and/or pathology report
Ki-67 testing, which is considered part of standard of care in the pathology report, must have been performed between 14 and 90 days prior to registration and the result must be >= 3% and =< 55%. Treating investigators are encouraged to contact the S2104 Study Chairs and/or the study pathology chair with questions. If more than one Ki-67 is reported (e.g., primary tumor versus lymph node or metastatic site), the highest one should be considered for the study eligibility criteria
Participants with localized resected pNETS must have a Zaidi score of >= 3 derived by the following factors and points:

1 point; symptomatic tumor defined as one of the following:

Gastrointestinal bleed
Jaundice
Gastrointestinal obstruction
Pain from primary tumor prior to surgical resection
Pancreatitis
2 points; primary pancreas tumor size > 2 cm
1 point; Ki-67 3% to 20%
1 point; lymph node positivity = 1
6 points; Ki-67 21% to 55%
Participants may have received resection/ablation of liver oligo-metastatic disease (up to 5 liver metastases) at the time of well-differentiated pNET resection
Participants must have recovered from effects of surgery as determined by the treating investigator
Participants must be >= 18 years old
Participants must have Zubrod performance status of 0-2
Participants must have a complete medical history and physical exam within 28 days prior to registration
Leukocytes >= 3 x 10^3/uL (within 28 days prior to registration)
Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to registration)
Platelets >= 100 x 10^3/uL (within 28 days prior to registration)
Total bilirubin =< institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to registration)
Serum creatinine =< 1.5 x institutional ULN (within 28 days prior to registration)
Calculated creatinine clearance >= 50 ml/min (within 28 days prior to registration)
Participants must be able to swallow pills
Participants must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol
No other active malignancy or history of prior malignancy is allowed, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

Participants must not have unresected or unablated metastatic disease
Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis
Participants must not have received prior neoadjuvant therapy for treatment of pancreatic neuroendocrine tumor. Use of somatostatin analogs prior to surgery is permitted
Participants must not have received somatostatin analogs after surgery
Participants must not be planning to receive warfarin while on protocol treatment. Other anticoagulants are allowed
Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine
Participants must not have known absorption issues that would limit the ability to absorb study agents
Participants must not have had an arterial thromboembolic event, unstable angina, or myocardial infarction within 12 months prior to registration
Participants must not have active or uncontrolled infection
Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator
Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Heloisa P Soares, SWOG Cancer Research Network

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record