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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 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: November 11, 2014
Last verified: November 2014

April 2, 2013
November 11, 2014
May 2013
December 2014   (final data collection date for primary outcome measure)
PFS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
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.
Complete list of historical versions of study NCT01824875 on ClinicalTrials.gov Archive Site
  • RR defined by revised 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 Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • 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 ]
Not Provided
Not Provided
 
Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors
A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors

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, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether temozolomide is more effective with or without capecitabine in treating patients with advanced pancreatic neuroendocrine tumors.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Gastrinoma
  • Glucagonoma
  • Insulinoma
  • Islet Cell Carcinoma
  • Pancreatic Polypeptide Tumor
  • Recurrent Islet Cell Carcinoma
  • Somatostatinoma
  • 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
  • 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.
    Interventions:
    • Drug: temozolomide
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: temozolomide
    • Drug: capecitabine
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
145
Not Provided
December 2014   (final data collection date for primary outcome measure)

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)
  • Date of last documented disease progression must be =< 12 months from date of randomization
  • Patient must not have received prior temozolomide, dacarbazine (DTIC), or capecitabine, or 5-FU (fluorouracil) therapy
  • Prior everolimus and/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 glutamate pyruvate transaminase [SGPT]) =< 3 X institutional ULN or (=< 5 X institutional ULN if the patient has liver metastases)
  • Serum creatinine =< 1.5 X institutional ULN
  • 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 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:

    • 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 magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol
Both
18 Years and older
No
United States
 
NCT01824875
E2211, NCI-2012-02007, E2211, E2211, U10CA021115, U10CA180820
Yes
Eastern Cooperative Oncology Group
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Pamela Kunz ECOG-ACRIN Cancer Research Group
Eastern Cooperative Oncology Group
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP