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Active, not recruiting Phase 2

Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced Poorly Differentiated (G3) Non-Small Cell Gastrointestinal Neuroendocrine Carcinomas

NCT02595424 · tracked via the Priya Life Science Israel tracker
Phase
Phase 2
Started
2015-11-06
Last updated
2026-10-02

Condition(s) studied

Gastric Neuroendocrine CarcinomaIntestinal Neuroendocrine CarcinomaPancreatic Neuroendocrine Carcinoma

Investigational drug(s) / intervention(s)

Capecitabine →Carboplatin →Cisplatin →Etoposide →Laboratory Biomarker AnalysisTemozolomide →

Capecitabine: Given PO

Carboplatin: Given IV

Cisplatin: Given IV

Etoposide: Given IV

Laboratory Biomarker Analysis: Correlative studies

Temozolomide: Given PO

Study summary

This randomized phase II trial studies how well temozolomide and capecitabine work compared to standard treatment with cisplatin or carboplatin 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, carboplatin 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 or carboplatin and etoposide in treating patients with this type of neuroendocrine carcinoma, called non-small cell neuroendocrine carcinoma.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: * Patients must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma that is either known or suspected to be of gastrointestinal (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 Response Evaluation Criteria in Solid Tumors (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 computed tomography (CT) or contrast magnetic resonance imaging (MRI) * NOTE: positron emission tomography (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 * Any prior surgeries must have been completed at least 4 weeks prior to randomization * Patients must have an Eastern Cooperative Oncology Group (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 * 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 \[SGPT\]) =\< 2.5 X institutional ULN or (=\< 5 X institutional ULN if the patient has liver metastases) * Serum creatinine =\< 1.5 X institutional ULN and creatinine clearance \>= 60 ml/min * 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 impaired decision-making capacity may participate in the study if a legal authorized representative is available to consent * 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 magnetic resonance (MR) imaging including contrast agents as required for the treatment and the protocol Exclusion Criteria: * Patients may not have had any prior systemic treatment for this malignancy (for example chemotherapy or somatostatin analogues); 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 * Patients with brain metastases (either remote or current) or presence of carcinomatous meningitis are not eligible * Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency will be excluded * 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 * 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 * Unstable angina * Myocardial Infarction * 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 * Women must not be pregnant or breast-feeding * 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 not undergone a hysterectomy or bilateral oophorectomy; or 2) 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) * Patients who are known to have human immunodeficiency virus (HIV) or are on combination antiretroviral therapy are ineligible

Primary outcome measure(s)

  • Progression-free Survival (PFS) — assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years from randomization until disease progression, up to 5 years from study registration
    PFS is defined as the time from randomization to documented progression or death without progression. PFS is censored at the date of last disease evaluation. The study was closed for futility in 2021 after the 2021 Spring DSMC meeting, which found that the boundary for futility had been met (ie, temozolomide and capecitabine did not appear to be superior to platinum and etoposide chemotherapy). As the interim analysis finding led to the conclusion of the study, no PFS stratified logrank test was conducted with the data extracted on April 23rd, 2025 for the final analysis, that was presented here.

Trial sites (673)

FacilityCityRegionStatus
Kingman Regional Medical Center Kingman Arizona
Cancer Center at Saint Joseph's Phoenix Arizona
Mercy Hospital Fort Smith Fort Smith Arkansas
CHI Saint Vincent Cancer Center Hot Springs Hot Springs Arkansas
Kaiser Permanente-Deer Valley Medical Center Antioch California
Mission Hope Medical Oncology - Arroyo Grande Arroyo Grande California
PCR Oncology Arroyo Grande California
Sutter Auburn Faith Hospital Auburn California
Sutter Cancer Centers Radiation Oncology Services-Auburn Auburn California
Alta Bates Summit Medical Center-Herrick Campus Berkeley California
Mills-Peninsula Medical Center Burlingame California
Sutter Cancer Centers Radiation Oncology Services-Cameron Park Cameron Park California
Eden Hospital Medical Center Castro Valley California
Sutter Davis Hospital Davis California
Kaiser Permanente Dublin Dublin California
Kaiser Permanente-Fremont Fremont California
Palo Alto Medical Foundation-Fremont Fremont California
Kaiser Permanente-Fresno Fresno California
Los Angeles County-USC Medical Center Los Angeles California
USC / Norris Comprehensive Cancer Center Los Angeles California
Cedars Sinai Medical Center Los Angeles California
Memorial Medical Center Modesto California
Kaiser Permanente-Modesto Modesto California
Palo Alto Medical Foundation-Camino Division Mountain View California
Palo Alto Medical Foundation-Gynecologic Oncology Mountain View California
USC Norris Oncology/Hematology-Newport Beach Newport Beach California
Sutter Cancer Research Consortium Novato California
Kaiser Permanente-Oakland Oakland California
Palo Alto Medical Foundation Health Care Palo Alto California
Stanford Cancer Institute Palo Alto Palo Alto California
Keck Medical Center of USC Pasadena Pasadena California
Eisenhower Medical Center Rancho Mirage California
Kaiser Permanente-Redwood City Redwood City California
Kaiser Permanente-Richmond Richmond California
Kaiser Permanente-Roseville Roseville California
Sutter Cancer Centers Radiation Oncology Services-Roseville Roseville California
Sutter Roseville Medical Center Roseville California
Kaiser Permanente Downtown Commons Sacramento California
Sutter Medical Center Sacramento Sacramento California
Kaiser Permanente-South Sacramento Sacramento California

+ 633 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT02595424 on ClinicalTrials.gov ↗ ← All trials in Israel