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What is SWOG S2104?

A Randomized Phase II Trial of Postoperative Adjuvant Capecitabine and Temozolomide Versus Observation in High-Risk Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (pNETS) account for about 1-2% of all the pancreas tumors for which resection is the only curative intent modality, however, despite surgery, many patients will experience recurrence. Tumor size, positive lymph nodes and higher grade are prognostic factors for recurrence. The U.S. Neuroendocrine Tumor Study Group published a predictive score (Zaidi score but also see inclusion criteria) demonstrating that tumors with a score ≥6 had a 33% likelihood of recurrence by 24 months. Furthermore, it is known that that patients with metastatic disease who undergo curative intent resection also have a great risk of recurrence. Despite these known risk factors for recurrence, to date, no prospective study exploring the role of adjuvant cytotoxic chemotherapy has ever been performed in this population. Supported by the E2211 results using capecitabine and temozolomide (CAPTEM) in the metastatic setting, S2104 investigates the role of CAPTEM in the adjuvant setting.

The clinical trial is taking place across multiple sites in US and completed primary endpoint estimate is 31 Mar 2025 (see clinical trials doc below)

Trial Purpose and Description

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.

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

Why is this trial important? 

There is no proven additional treatment after surgery for people with high-risk pancreatic neuroendocrine tumors. Most often, doctors watch a patient’s condition after surgery and treat symptoms as needed. This trial is a way to find out if chemotherapy after surgery is a better treatment plan for people with high-risk tumors.

Read more here

1.  SWOG Description
2. ClinicalTrials.gov Identifier – NCT05040360
3. Zaidi score – see here 

General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact.  If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net

The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan. 

 
 

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional. Some content may be generated by AI which can sometimes be misinterpreted.  Please check any references attached.    

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

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