Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


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

- 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

- 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 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 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

- 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)

- 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

- Patients who are known to have human immunodeficiency virus (HIV) or are on
combination antiretroviral therapy are ineligible

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A (capecitabine, temozolomide)
Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Capecitabine
    Given PO
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Temozolomide
    Given PO
Active Comparator
Arm B (cisplatin, carboplatin, etoposide)
Patients receive cisplatin 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.
  • Drug: Carboplatin
    Given IV
  • Drug: Cisplatin
    Given IV
  • Drug: Etoposide
    Given IV
  • Other: Laboratory Biomarker Analysis
    Correlative studies

Recruiting Locations

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
Contact:
Site Public Contact
210-450-3800
phoresearchoffice@uthscsa.edu

More Details

Status
Recruiting
Sponsor
ECOG-ACRIN Cancer Research Group

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.