Clinical Trials /

Study of Capecitabine-Temozolomide(CapTem) With Yttrium-90 in Patients With Unresectable Metastatic Grade 2 Neuroendocrine Tumors

NCT04339036

Description:

This is a Phase 2 evaluation of hepatic-progression free survival among patients with Grade 2 liver-dominant NET metastases undergoing combination therapy with CapTem and Y90 radioembolization.The hypothesis is to confirm safety and to assess if disease control is improved relative to expectation from either therapy alone.

Related Conditions:
  • Neuroendocrine Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Capecitabine-Temozolomide(CapTem) With Yttrium-90 in Patients With Unresectable Metastatic Grade 2 Neuroendocrine Tumors
  • Official Title: UPCC 04219 Phase 2 Study of Capecitabine-Temozolomide(CapTem) With Yttrium-90 Radioembolization in the Treatment of Patients With Unresectable Metastatic Grade 2 Neuroendocrine Tumors

Clinical Trial IDs

  • ORG STUDY ID: 833304
  • NCT ID: NCT04339036

Conditions

  • Neuroendocrine Tumor Grade 2
  • Neuroendocrine Tumors

Interventions

DrugSynonymsArms
Capecitabine Oral ProductXelodaOral CapTem + Y90 Radioembolization
Temozolomide Oral ProductTemodarOral CapTem + Y90 Radioembolization

Purpose

This is a Phase 2 evaluation of hepatic-progression free survival among patients with Grade 2 liver-dominant NET metastases undergoing combination therapy with CapTem and Y90 radioembolization.The hypothesis is to confirm safety and to assess if disease control is improved relative to expectation from either therapy alone.

Trial Arms

NameTypeDescriptionInterventions
Oral CapTem + Y90 RadioembolizationExperimentalCapecitabine 750 mg/m2 twice daily orally for 14 days and temozolomide 200 mg/m2 orally on Days 10-14, with 14 days between cycles, to be continued until 1) disease progression or 2) intolerable toxicities. Trans-arterial radioembolization (TARE) on Day 7 of cycle 2 and, if needed for the other lobe, Day 7 of either cycle 3 or 4.
  • Capecitabine Oral Product
  • Temozolomide Oral Product

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with confirmed diagnosis of histologic grade 2 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 > 1cm (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

          -  Age >18 years.

          -  Life expectancy of greater than 6 months.

          -  ECOG performance status 0-2.

          -  Adequate liver function as measured by: Total bilirubin ≤ 2.0mg/dl, ALT, AST ≤5 times
             ULN, albumin ≥2.5g/dl.

          -  Patients must have adequate organ and marrow function as defined below:

          -  platelets >100,000/mcL (may be corrected by transfusion)

          -  serum creatinine < 2.0 mg/dl

          -  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 urine or serum βHCG for women of child-bearing age)

        Exclusion Criteria:

          -  Contraindications to capecitibine or temozolomide

          -  Contraindicated for both contrast-enhanced MRI and 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 (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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Intra-hepatic progression-free survival
Time Frame:2 years. Time from initiation of study therapy until first documented intra-hepatic disease progression, death due to any cause or last scan date that documented intra-hepatic progression-free status.
Safety Issue:
Description:Intra-hepatic progression-free survival by RECIST 1.0 is defined as the time from initiation of study therapy until first documented intra-hepatic disease progression, death due to any cause or last scan date that documented intra-hepatic progression-free status.

Secondary Outcome Measures

Measure:Overall Progression free survival
Time Frame:2 years. time from initiation of study therapy until first documented intra- or extra-hepatic disease progression, death due to any cause or last scan date that documented progression-free status
Safety Issue:
Description:Overall progression-free survival is defined as the time from initiation of study therapy until first documented intra- or extra-hepatic disease progression, death due to any cause or last scan date that documented progression-free status
Measure:Intra-hepatic tumor responses
Time Frame:2 years. from time of initiation of study therapy until subject comes off of study, or study closes
Safety Issue:
Description:Intra-hepatic tumor responses will be evaluated by EASL criteria and RECIST.
Measure:extra-hepatic tumor responses
Time Frame:2 years. from time of initiation of study therapy until subject comes off of study, or study closes
Safety Issue:
Description:extra-hepatic tumor responses will be evaluated by RECIST.
Measure:Systemic toxicities
Time Frame:From period of enrollment to 24 months after last treatment
Safety Issue:
Description:Systemic toxicities will be individually assessed by NCI CTCAE Version 4.
Measure:Hepatic toxicities
Time Frame:From period of enrollment to 24 months after last treatment
Safety Issue:
Description:Hepatic toxicities will be individually assessed by NCI CTCAE Version 4.
Measure:Tumor markers
Time Frame:Tumor markers will be assessed at baseline and then every 3 months for 24 months.
Safety Issue:
Description:The primary marker is CgA. Additional cancer site-specific (i.e., gastrinoma) markers may also be assayed.
Measure:Quality of Life by EORTC QLQ - GI.NET21.
Time Frame:Quality of life will be measured at baseline and then every 3 months for 24 months .
Safety Issue:
Description:Quality of Life will be measure by a validated NET-specific instrument, EORTC QLQ - GI.NET21.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

April 7, 2020