E2211:A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients with Advanced Pancreatic Neuroendocrine Tumors
- Clements University Hospital
Muhammad Beg, M.D.
This is a multi-institutional randomized study of temozolomide administered with or without capecitabine in advanced pancreatic neuroendocrine tumor patients. The purpose of this study is to compare the effects, good and/or bad, of temozolomide versus temozolomide plus capecitabine on advanced pancreatic neuroendocrine tumor cancer to find out which is better.
Temozolomide 200mg/m2 po QD days 1-5
CT Scans every 3 cycles
Capecitabine 750 mg/m po BiD days 1-14
Temozolomide 200 mg/m po QD days 10-14
CT scans every 3 cycles
Patients will be randomized with equal probability to treatment with single agent temozolomide or the combination of temozolomide and capecitabine using a stratified permuted blocks algorithm with stratification based on prior treatment with everolimus (Yes vs no), prior treatment with sunitinib (Yes vs no) and concurrent administration of octreotide (Yes vs no).
*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 RECIST 1.1 criteria as defined in Section 6.1.2. 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 MRI.
*Patient must have documented disease progression, and date of last documented disease progression must be within 12 months from date of randomization.
*Patient must not have received prior temozolomide, DTIC, capecitabine, or 5-FU 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 patient 1) have been on stable dose (+/- 10mg) for 8 weeks and 2) has documented disease progression on that dose.
*Chemoembolization is allowed if >= 4 weeks from study entry. There are 3 possible scenarios:
-If patient has hepatic disease only: they need to have progressed in the liver since chemoembolization and have measureable disease by RECIST 1.1 in order to be eligible.
-If patient has hepatic and extrahepatic disease: they will need to have progressed inside OR outside the liver and have measureable disease by RECIST 1.1 in order to be eligible.
*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.
*Patients must have normal organ and marrow function as defined below within <= 14 days prior to randomization:
-Leukocytes >= 3,000/mm3
-Absolute neutrophil count >= 1,500/mm3
-Hemoglobin >= 9 g/dL
-Platelets >= 100,000/mm
-Total bilirubin <= institutional upper limit of normal (ULN) or <= 1.5 X institutional ULN (if the patient has liver metastases).
-AST(SGOT)/ALT(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 be at least 18 years of age.
*Patient must have ECOG-ACRIN 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
*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.
* 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 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: 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. 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.