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Randomized Phase II Study of Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced G3 Non-small Cell Gastroenteropancreatic Neuroendocrine Carcinomas

Overall Recruitment Status: Active, currently enrolling

Official Title

Randomized Phase II Study of Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced G3 Non-small Cell Gastroenteropancreatic Neuroendocrine Carcinomas

Region

Sponsors

California - Northern

ECOG-ACRIN Cancer Research Group

Acronym

NCT No.

EA2142

NCT02595424

Study Type

Phase

INTERVENTIONAL

Phase II

Purpose

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.

Detailed Description

PRIMARY OBJECTIVES: I. To assess the progression free survival (PFS) of platinum (cisplatin or carboplatin) and etoposide versus the PFS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. SECONDARY OBJECTIVES: I. To assess the response rate (RR) of platinum (cisplatin or carboplatin) and etoposide versus the RR of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. II. To assess the overall survival (OS) of platinum (cisplatin or carboplatin) and etoposide versus the OS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. III. To evaluate the toxicities associated with the combination of temozolomide and capecitabine and the combination of platinum (cisplatin or carboplatin) and etoposide, respectively, in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. TERTIARY OBJECTIVES: I. To assess the impact of each treatment regimen on PFS, RR and OS based on marker of proliferation Ki-67 index in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. (Laboratory) II. To assess the prognostic significance of well differentiated versus poorly differentiated non-small cell gastroenteropancreatic neuroendocrine tumors in relationship to survival and response to treatment. (Laboratory) III. To assess the agreement in Ki-67 status between that reported by institutional pathologist and that reported by central pathology review. (Laboratory) OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14 and temozolomide PO once daily (QD) on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive cisplatin intravenously (IV) on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Inclusion Criteria

Patients must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma of the gastrointestinal (GI) tract

Patients must have pathologically/histologically confirmed tumor of non-small cell histology

Patients must have a Ki-67 proliferative index of 20-100%

Patients must have evidence of at least 10 mitotic figures per 10 high powered fields

Patients must have tissue available for central pathology review

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: PET-CT scans are allowed provided the CT portion is of the same diagnostic quality, with IV contrast. Patients may not have had any prior treatment for this malignancy

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 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)

Please contact study team for more eligibility criteria

Exclusion Criteria

Please contact study team for more eligibility criteria

Keywords and/or Specific Medical Conditions

Esophageal	Large Cell Neuroendocrine Carcinoma
Colorectal	Pancreatic
EA2142	Small Intestinal
Gallbladder Large Cell Neuroendocrine Carcinoma	Oncology (Adult)
Gastric Large Cell Neuroendocrine Carcinoma

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