Cisplatin and Etoposide or Temozolomide and Capecitabine in Treating Patients With Neuroendocrine Carcinoma of the Gastrointestinal Tract or Pancreas That Is Metastatic or Cannot Be Removed by Surgery

Overview

About this study

This randomized phase II trial studies how well temozolomide and capecitabine work compared to standard treatment with cisplatin and etoposide in treating patients with neuroendocrine carcinoma of the gastrointestinal tract or pancreas that has spread to other parts of the body (metastatic) or cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, capecitabine, cisplatin, and etoposide, 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. Certain types of neuroendocrine carcinomas may respond better to treatments other than the current standard treatment of cisplatin and etoposide. It is not yet known whether temozolomide and capecitabine may work better than cisplatin and etoposide in treating patients with this type of neuroendocrine carcinoma, called non-small cell neuroendocrine carcinoma.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

 

  • Patients must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma that is either known or suspected to be of GI origin. Primary tumors arising from the lung, gynecologic organs or prostate are not permitted.
  • Patients must have pathologically/histologically confirmed tumor of non-small cell histology.
  • Patients must have a Ki-67 proliferative index of 20-100% OR at least 10 mitotic figures per 10 high powered fields
  • Patients must have measurable disease by RECIST 1.1 criteria. Baseline measurements and evaluations of all sites of disease must be obtained within 4 weeks prior to randomization and must be acquired by multiphasic CT or contrast MRI.
    • NOTE: PET-CT scans are allowed provided the CT portion of the exam is equivalent to a diagnostic CT scan and includes both oral and IV contrast.
  • Patients may not have had any prior systemic therapy (chemotherapy, targeted therapy, PRRT) for this malignancy. Prior somatostatin therapy is permitted. Prior palliative radiation is permitted but radiated lesions may not be used for measurement.
  • Patients may not have received any of the protocol agents within 5 years prior to randomization.
  • Any prior surgeries must have been completed at least 4 weeks prior to randomization.
  • Patients must be at least ≥ 18 years of age.
  • Patients must have an ECOG performance status of 0-2.
  • Patients may not be receiving any other investigational agents while on study treatment.
  • Patients may not be receiving Coumadin while on treatment. Other anticoagulants are allowed.
  • Patients must have normal organ and marrow function as definded below within less than or equal to 14 days prior to randomization:
    • Leukocytes ≥ 3,000/mm^3
      • Leukocytes ________ Date: ________
    • Absolute neutrophil count ≥ 1,500/mm3
      • Neutrophil count: ________ Date: ________
    • Hemoglobin ≥ 9 g/dL
      • Hemoglobin: ________ Date: ________
    • Platelets ≥ 100,000/mm^3
      • Platelets: ________ Date: ________
    • Total bilirubin ≤ institutional upper limit of normal (ULN) or ≤ 1.5 X institutional ULN (if the patient has liver metastases).
      • ULN: ________ Bilirubin: ________ Date: ________
    • AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional ULN or (≤ 5 X institutional ULN if the patient has liver metastases).
      • ULN: ________ AST ________ Date: ________
      • ULN: ________ ALT ________ Date: ________
    • Serum creatinine ≤ 1.5 X institutional ULN and creatinine clearance ≥ 60 ml/min
      • ULN: ________ Creatinine: ________ Date: ________
      • NOTE: Creatinine Clearance must be calculated using the Cockcroft-Gault equation.
  • Patients must have a life expectancy of ≥ 12 weeks as determined clinically by the treating physician.
  • Patients with brain metastases (either remote or current) or presence of carcinomatous meningitis are not eligible.
  • Patients with known DPD deficiency will be excluded as the use of capecitabine is contraindicated in these patients.
  • Patients must NOT have active or uncontrolled infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia or a serious psychiatric illness/social situation that would limit compliance with study requirements.
  • Non-melanoma skin cancer, in situ cervical cancer, superficial bladder cancer, or breast cancer in situ. 
  • Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years. 
  • Prior malignancy cured by non-surgical modalities and patient has been continuously disease free for > 5 years.
  • Patients with impaired decision making capacity may participate in the study if a legal authorized representative is available to consent.
  • Patients must NOT have a history of allergic reactions attributed to compounds of similar chemical or biochemical composition to cisplatin, carboplatin, etoposide, temozolomide or capecitabine.
  • Patients must NOT have absorption issues that would limit the ability to absorb study agents.
  • Patients with a history of the following within ≤ 12 months of study entry are not eligible:
    • Arterial thromboembolic events: Yes: ____ Date: ________ No: ____
    • Unstable angina: Yes: ____ Date: ________ No: ____
    • Myocardial Infarction: Yes: ____ Date: ________ No: ____
  • Patients with symptomatic peripheral vascular disease are not eligible.
  • Patients must NOT have previous or concurrent malignancy. Exceptions are made for patients who meet any of the following conditions:
    • Non-melanoma skin cancer, in situ cervical cancer, superficial bladder 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.
    • Date of last evidence of disease: ________
  • Women must not be pregnant or breast-feeding due to potential harm to the fetus from cisplatin, carboplatin, etoposide, temozolomide and/or capecitabine.
    • 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: 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
    • Female of child bearing potential? ______ (Yes or No)
    • Date of blood test or urine study: ___________
  • 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.
  • Patients must be able to swallow pills.
  • Patients must be able to tolerate CT or MR imaging including contrast agents as required for the treatment and the protocol.
  • Patients who are known to have HIV or are on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cisplatin, carboplatin, etoposide, temozolomide, and/or capecitabine. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Thorvardur Halfdanarson, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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