Capecitabine and Temozolomide Versus Observation in Pancreatic Neuroendocrine Tumors

What is the Purpose of this Study?

This study focuses on people who have had surgery for pancreatic neuroendocrine tumor (pNET), a type of cancer that forms tumors in the pancreas. The purpose of the study is to determine whether giving chemotherapy after surgery will lower the chance of pNET returning, compared to the usual approach. The usual approach for patients who are not in a study is surgery followed by observation. Participants will be randomly assigned to receive the drugs capecitabine and temozolomide for up to 4 months or the usual approach of observation only. Capecitabine and temozolomide could prevent or delay recurrence of cancer but could also cause side effects. Capecitabine and temozolomide are approved by the U.S. Food and Drug Administration (FDA) for use various conditions, but their use in pNET is considered investigational.

Eligibility

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

Inclusion Criteria:

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

Exclusion Criteria:

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

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Where can I participate?

Cedars-Sinai Cancer at SOCC : Abrahm Levi

More about this Clinical Trial

What is the full name of this clinical trial?

S2104: Randomized Phase II Trial of Postoperative Adjuvant Capecitabine and Temozolomide versus Observation in High-Risk Pancreatic Neuroendocrine Tumors

Study Details

Disease Type/Condition

Other Digestive Organ

Principal Investigator

Hendifar, Andrew

Co-Investigators

Arsen Osipov, Jun Gong, Kamya Sankar

Age Group

Adult

Phase

IRB Number

STUDY00003358

ClinicalTrials.gov ID

NCT05040360

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Abrahm Levi

Abrahm.Levi@cshs.org