Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Eastern Cooperative Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01824875
First received: April 2, 2013
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

This randomized phase II trial studies how well giving temozolomide with or without capecitabine works in treating patients with advanced pancreatic neuroendocrine tumors. Drugs used in chemotherapy, such as temozolomide and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether temozolomide is more effective with or without capecitabine in treating patients with advanced pancreatic neuroendocrine tumors.


Condition Intervention Phase
Gastrinoma
Glucagonoma
Insulinoma
Islet Cell Carcinoma
Pancreatic Polypeptide Tumor
Recurrent Islet Cell Carcinoma
Somatostatinoma
Drug: temozolomide
Drug: capecitabine
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • PFS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    There will be two log-rank tests conducted, an interim analysis at 76% information and a final analysis at 100% information (105 PFS events), projected to occur at 3 years from the start of accrual. The overall type I error will be controlled using an O'Brien-Fleming boundary function. If the repeated two-sided 95% confidence interval on the hazard ratio does not contain the target alternative hazard ratio of 0.64, consideration will be given to declaring the study negative and reporting the results.


Secondary Outcome Measures:
  • RR defined by revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Compared between arms using a two-group Fisher's exact test at an overall two-sided 20% significance level. In addition, within each arm, a 90% confidence interval on the true objective response rate will be no wider than 21 percentage points.

  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Toxicity rates using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 145
Study Start Date: April 2013
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (temozolomide)
Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (temozolomide and capecitabine)
Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.

SECONDARY OBJECTIVES:

I. To evaluate response rates (RR) associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.

II. To evaluate overall survival (OS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.

III. To evaluate the toxicity associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.

IV. To evaluate the usefulness of methyl guanine methyltransferase (MGMT) status (by immunohistochemistry [IHC] and promoter methylation) for predicting response in pancreatic neuroendocrine tumor patients treated with either temozolomide or temozolomide and capecitabine.

V. To bank radiology images for evaluation of quality, reproducibility, and compliance with computed tomography (CT) methodology.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive capecitabine PO twice daily (BID) on days 1-14 and temozolomide PO QD on days 10-14. Treatment repeats every 28 days for up to 13 courses 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have histologically or pathologically confirmed locally unresectable or metastatic low or intermediate grade pancreatic neuroendocrine tumor, excluding small cell carcinoma
  • Patient 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 =< 4 weeks prior to randomization and must be acquired by multiphasic CT or contrast magnetic resonance imaging (MRI)
  • Randomization must occur =< 12 months of last documented disease progression
  • Patient must not have received prior temozolomide, dacarbazine (DTIC), or capecitabine, or 5-FU (fluorouracil) therapy
  • Prior everolimus or sunitinib therapy is allowed, so long as it was discontinued >= 4 weeks prior to randomization
  • Concurrent somatostatin analogues are allowed provided that patients

    • Have been on stable doses for 8 weeks and
    • Have documented disease progression on that dose
  • 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 glutamic pyruvate transaminase [SGPT]) =< 3 X institutional ULN or (=< 5 X institutional ULN if the patient has liver metastases)
  • Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patient must have life expectancy >= 12 weeks
  • Patients with either clinically apparent central nervous system metastases or carcinomatous meningitis are ineligible
  • Patients must NOT have active or uncontrolled infection or serious medical or psychiatric illness
  • Patients must NOT have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine
  • Patient 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, or breast cancer in situ OR
    • Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years
  • Women must not be pregnant or breast-feeding due to potential harm to fetus from 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:

    • Has not undergone a hysterectomy or bilateral oophorectomy; or
    • 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; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
  • Patient must be able to swallow pills
  • Patient must be able to tolerate CT or MR imaging including contrast agents as required for their treatment and the protocol
  Contacts and Locations
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 below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01824875

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group Recruiting
Boston, Massachusetts, United States, 02215
Contact: Pamela L. Kunz    650-725-9057    pkunz@stanford.edu   
Principal Investigator: Pamela L. Kunz         
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Pamela Kunz Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01824875     History of Changes
Other Study ID Numbers: E2211, NCI-2012-02007, U10CA021115
Study First Received: April 2, 2013
Last Updated: February 4, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Gastrinoma
Zollinger-Ellison Syndrome
Glucagonoma
Insulinoma
Somatostatinoma
Neuroendocrine Tumors
Adenoma, Islet Cell
Carcinoma, Islet Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paraneoplastic Endocrine Syndromes
Paraneoplastic Syndromes
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Intestinal Diseases
Peptic Ulcer
Stomach Diseases
Adenoma
Carcinoma, Neuroendocrine
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on August 28, 2014