CapTemY90 for Grade 2 NET Liver Metastases

Neuroendocrine Tumors Clinical Trial

— CapTemY90  

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04339036
• Other study ID #: 833304
• Status: Recruiting
• Phase: Phase 2
• Start date: October 7, 2021
• Est. completion date: May 1, 2026

Study information

• Verified date: December 2023
• Source: Abramson Cancer Center at Penn Medicine
• Contact: Michael Soulen, MD
• Phone: 855-216-0098
• Email: michael.soulen[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Patients with liver-dominant Grade 2 NET metastases from any primary will start CapTem and undergo simulation angiography for radioembolization planning during the first cycle. If they tolerate CapTem and are not excluded from radioembolization, then TARE will be performed on Day 7 of Cycle 2, with additional TARE of Day 7 of cycle 3 or 4 as needed to treat the entire tumor burden. Patients will remain on CapTem until progression or intolerance.

Primary outcome measure is hepatic progression-free survival.

Other known NCT identifiers

• NCT04789109

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: May 1, 2026
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ßHCG 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

Related Conditions & MeSH terms

• Neoplasms
• Neuroendocrine Tumor Grade 2
• Neuroendocrine Tumors

Intervention

Drug:
• Capecitabine Oral Product
Capecitabine 750 mg/m2 twice daily orally for 14 days
• Temozolomide Oral Product
temozolomide 200 mg/m2 orally on Days 10-14, with 14 days between cycles

Combination Product:
• transarterial radioembolization
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.

Locations

Country	Name	City	State
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	CARTI Cancer Center	Little Rock	Arkansas
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Abramson Cancer Center at Penn Medicine	CARTI, Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

References & Publications (24)

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* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intra-hepatic progression-free survival	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.	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.
Secondary	Overall Progression free survival	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	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
Secondary	Intra-hepatic tumor responses by RECIST	Intra-hepatic tumor responses will be evaluated by RECIST.	2 years. from time of initiation of study therapy until subject comes off of study, or study closes
Secondary	Intra-hepatic tumor responses by EASL	Intra-hepatic tumor responses will be evaluated by EASL criteria.	2 years. from time of initiation of study therapy until subject comes off of study, or study closes
Secondary	extra-hepatic tumor responses	extra-hepatic tumor responses will be evaluated by RECIST.	2 years. from time of initiation of study therapy until subject comes off of study, or study closes
Secondary	Number of participants with systemic toxicities	Systemic toxicities will be individually assessed by NCI CTCAE Version 4.	From period of enrollment to 24 months after last treatment
Secondary	Number of participants with hepatic toxicities	Hepatic toxicities will be individually assessed by NCI CTCAE Version 4.	From period of enrollment to 24 months after last treatment
Secondary	Change in CgA over time	The primary marker is CgA. Additional cancer site-specific (i.e., gastrinoma) markers may also be assayed.	Tumor markers will be assessed at baseline and then every 3 months for 24 months.
Secondary	Quality of Life by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Neuroendocrine tumor	Quality of Life will be measure by a validated NET-specific instrument, EORTC. Scale is 0-100, higher scores indicate worse symptoms/functioning	Quality of life will be measured at baseline and then every 3 months for 24 months .