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Capecitabine and Temozolomide with A Specific Form of Radiation Therapy (Transarterial Radioembolization) for the Treatment of Unresectable Grade II/III Neuroendocrine Tumors with Liver Metastases
Trial Status: active
This phase II trial studies how well capecitabine and temozolomide (CapTem) with transarterial radioembolization (TARE) work for the treatment of grade II/III neuroendocrine tumors (NET) that cannot be removed by surgery (unresectable) and have spread to the liver (liver metastases). Drugs used in chemotherapy, such as capecitabine and temozolomide, 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. Capecitabine and temozolomide are “radiosensitizers”, meaning that they help radiation treatment work better, and are often used in combination with radiation therapy for some types of cancer. Radioembolization is a type of radiation therapy used to treat liver cancer or cancer that has spread to the liver. Giving capecitabine and temozolomide with transarterial radioembolization may help improve tumor control in the liver.
Inclusion Criteria
Patients with confirmed diagnosis of histologic grade 2/3 neuroendocrine tumor with unresectable liver metastases (primary tumor or other extrahepatic disease may be present)
Patients with at least one measurable liver metastases, with size > 1 cm (Response Evaluation Criteria in Solid Tumors [RECIST] criteria)
Patients with liver dominant disease defined as >= 50% tumor body burden confined to the liver
Liver tumor burden does not exceed 50% of the liver volume
Patent main portal vein
At least 4 weeks since last administration of last chemotherapy and /or radiotherapy
Life expectancy of greater than 6 months
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Total bilirubin =< 2.0 mg/dl
Alanine aminotransferase (ALT), aspartate aminotransferase (AST ) =< 5 times upper limit of normal (ULN)
Albumin >= 2.5 g/dl
Platelets >= 100,000/mcL (may be corrected by transfusion)
Serum creatinine < 2.0 mg/dl
International normalized ratio (INR) < 1.6, (may be corrected by transfusion)
Ability to understand and the willingness to sign a written informed consent document
Women of child bearing potential and fertile men are required to use effective contraception (negative serum βHCG for women of child-bearing age)
Exclusion Criteria
Contraindications to capecitabine or temozolomide
Contraindicated for both contrast-enhanced magnetic resonance imaging (MRI) and computed tomography (CT)
Patients previously treated with transarterial embolization (with or without chemotherapy) or with radioembolization (Y-90 microspheres)
Contraindication for radioembolization procedures:
* Excessive hepatopulmonary shunt as determined by the investigator
* Inability to deliver Y90 microspheres without risk of non-target embolization of extra-hepatic structures
* Subjects consenting to the trial who fail their simulation angiography will be removed from the study and replaced
Patients may not be receiving any other investigational agents
Absolute contraindication to intravenous iodinated contrast (history [Hx] of significant previous contrast reaction, not mitigated by appropriate pre-medication)
Choledochoenteric anastomosis, transpapillary stent or sphincterotomy of duodenal papilla
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant and lactating women are ineligible
Additional locations may be listed on ClinicalTrials.gov for NCT04339036.
I. To estimate intra-hepatic progression-free survival and to test the hypothesis that the intra-hepatic progression free survival (PFS) rate at 18 months will be increased to 80%, compared to the published historical value of 60% for grade 2 NETs.
SECONDARY OBJECTIVES:
I. To estimate overall (intra- and extra-hepatic) progression-free survival.
II. To estimate intra-hepatic and extra-hepatic tumor response.
III. To describe systemic and local (hepatic) toxicities.
IV. To assess change in tumor markers.
V. To assess change in quality-of-life measures.
VI. To conduct exploratory correlative analyses of intra-hepatic and overall progression-free survival.
OUTLINE:
Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14 and temozolomide PO on days 10-14. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo trans-arterial radioembolization (TARE) of the dominant lobe on day 7 of cycle 2 and, if needed for the other lobe, also on day 7 of cycle 3 or 4. Patients undergo computed tomography (CT) scan, blood sample collection and may undergo magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up at 1 and 3 months and then every 3 months for 24 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUniversity of Pennsylvania/Abramson Cancer Center
