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Colon CancerPhase 1NCT02602327

Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

A Phase 1 study testing Tas-102 and SIR-Sphere in people with Colon Cancer and Rectal Cancer, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase I dose escalation study (3+3 design) with a dose expansion arm (12 patients) designed to evaluate safety of the combination of Tas-102 and radioembolization using Yttrium-90 (90Y) resin microspheres for patients with chemotherapy-refractory liver-dominant chemotherapy-refractory metastatic colorectal… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Cancer, Rectal Cancer, Liver Metastases
What is being tested?
Tas-102 and SIR-Sphere
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
9 Jan 2017to 31 Aug 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, 18 years of age or older, and of any ethnic or racial group.
  • Diagnosis of unresectable metastatic colorectal adenocarcinoma with liver-dominant bilobar disease. Diagnosis may be made by histo- or cyto-pathology, or by clinical and imaging criteria.
  • Disease progression or intolerance to at least two prior Food and Drug Administration-approved therapeutic regimens.
  • If extrahepatic disease is present, it must be asymptomatic.
  • If a primary tumor is in place, it must be asymptomatic.
  • Measurable target tumors using standard imaging techniques (RECIST v. 1.1 criteria).
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  • Tumor replacement < 50% of total liver volume.
  • Current Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 through screening to first treatment on study.
  • Completion of prior systemic therapy at least 14 days prior to enrollment.
  • Able to understand informed consent.

Who cannot join

  • At risk of hepatic or renal failure
  • Serum creatinine > 1.5 mg/dl
  • Serum bilirubin > 1.3 mg/ml
  • Albumin < 2.0 g/dL
  • Aspartate and/or alanine aminotransferase level > 5 times upper normal limit
  • Any history of hepatic encephalopathy
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  • Cirrhosis or portal hypertension
  • Clinically evident ascites (trace ascites on imaging is acceptable)
  • Contraindications to angiography and selective visceral catheterization
  • Any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device)
  • Severe allergy or intolerance to contrast agents, narcotics, or sedatives that cannot be managed medically
  • Symptomatic lung disease
  • Prior therapy with Tas-102.
  • Contraindications to Tas-102
  • Absolute neutrophil count < 1,500/μl
  • Platelet count < 75,000/μl
  • Allergy or intolerance to Tas-102
  • Unresolved toxicity of greater than or equal to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 2 due to prior therapies.
  • Evidence of potential delivery of
  • Greater than 30 Gy absorbed dose of radiation to the lungs during a single 90Y resin microsphere administration; or
  • Cumulative delivery of radiation to the lungs > 50 Gy over multiple treatments.
  • Evidence of any detectable Tc-99m macro aggregated albumin flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow.
  • Previous radiation therapy to the lungs and/or to the upper abdomen
  • Any prior arterial liver-directed therapy, including chemoembolization, bland embolization, and 90Y radioembolization
  • Any intervention for, or compromise of the ampulla of Vater
  • Active uncontrolled infection. Presence of latent or medication-controlled HIV and/or viral hepatitis is allowed.
  • Significant extrahepatic disease
  • Symptomatic extrahepatic disease (including primary tumor, if unresected).
  • Greater than 10 pulmonary nodules (each < 20 mm in diameter) or combined diameter of all pulmonary nodules > 15 cm.
  • Peritoneal carcinomatosis
  • Life expectancy less than 3 months
  • Pregnant or lactating female
  • In the investigator's judgment, any co-morbid disease or condition that would place the patient at undue risk and preclude safe use of radioembolization or Tas-102.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Phase I Study of Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

This is a phase I dose escalation study (3+3 design) with a dose expansion arm (12 patients) designed to evaluate safety of the combination of Tas-102 and radioembolization using Yttrium-90 (90Y) resin microspheres for patients with chemotherapy-refractory liver-dominant chemotherapy-refractory metastatic colorectal cancer (mCRC).

Read the detailed description

Randomized studies have demonstrated that Tas-102 has single agent activity against chemotherapy refractory colorectal cancer. A recent pre-clinical study has shown that Tas-102 may have activity as a radiation sensitizer in bladder cancer cell lines. Benefit of single agent Tas-102 against chemotherapy refractory colon cancer and the drug's promise a radiosensitizer make Tas-102 a potential candidate drug for testing in combination with radioembolization using Yttrium-90 resin microspheres in patients with liver-dominant chemotherapy-refractory mCRC. This is a phase I dose escalation study with a dose expansion arm designed to evaluate safety of the combination of Tas-102 and radioembolization using 90Y resin microspheres for patients with chemotherapy-refractory colon or rectal adenocarcinoma metastatic to the liver.

Being tested
Tas-102, SIR-Sphere
Keywords
radioembolization, Yttrium-90, 90Y, Resin microspheres, Tas-102, Lonsurf, SIR-Sphere
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tas-102Drug

    Also called Lonsurf

    Oral nucleoside antitumor agent consisting of α,α,α-trifluorothymidine (FTD) and 5-chloro-6-(2-iminopyrrolidin-1-yl) methyl-2,4 (1H,3H)-pyrimidinedione hydro chloride (TPI) at a molar ratio of 1:0.5.

  • SIR-SphereDevice

    Also called Yttrium-90 (Y90; 90Y) resin microspheres

    20-60mm resin microspheres containing Yttrium-90 (90Y, Y90) radioisotope

Study groups in NCT02602327
Study groupRoleWhat they receive
Tas-102 and radioembolizationExperimentalCombination therapy with Tas-102 and radioembolization using 90Y resin microspheres
Receives: Drug: Tas-102; Device: SIR-Sphere

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine dose limiting toxicities (DLT)

    Any adverse events grade ≥ 3 will be reviewed by the treating interventional radiologist and medical oncologist within 24 hours of being informed event. If none of the 3 patients in a cohort experiences a DLT, another 3 patients will be treated at the next higher dose level. However, if 1 of the first 3 patients experiences a DLT, 3 more patients will be treated at the same dose level. The dose escalation will continue until at least 2 patients among a cohort of 3-6 patients experience DLTs (i.e., ≥ 33% of patients with a dose-limiting toxicity at that dose level) or until 3-6 patients had been treated at TAS-102 dose of 35mg/m2 per day in 2 divided doses (up to a maximum of 80 mg per dose) administered concurrently with radioembolization cycles 1 and 2 without experiencing a DLT. DLT window will be 56 days (cycle 1, day 1 to cycle 2, day 28). Dose limiting toxicity will be reached when one of the clinical and/or laboratory parameters are met

    Measured: 56 days

  2. Maximum tolerated dose (MTD)

    Traditional 3+3 design will be used to determine the recommended dose for the dose expansion phase will be defined as the dose level just below this toxic dose level.

    Measured: Up to 4 years

Secondary outcomes (6)

  1. Overall response rate (ORR)

    Radiographic overall response rate (measured in accordance to Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) using imaging. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): 30% decrease in the sum of the longest diameter of target lesionsStable Disease (SD): Small changes that do not meet the criteria for CR, PR, or Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions. ORR will be defined as a ratio of the number of patients who demonstrated complete response (CR) or partial response (PR) to the number of all evaluated patients.

    Measured: Up to 4 years

  2. Progression-free survival (PFS)

    PFS will be defined as a time period that started at enrollment, during which a patient neither progressed nor died based on radiographic response.

    Measured: Up to 4 years

  3. Hepatic progression-free survival (HPFS)

    HPFS will be defined as a time period that started at enrollment, during which a patient neither progressed in the liver nor died based on radiographic response.

    Measured: Up to 4 years

  4. Extrahepatic progression free survival (EHPFS)

    EHPFS will be defined as a time period that started at enrollment, during which a patient neither progressed outside the liver nor died based on radiographic response

    Measured: Up to 4 years

  5. Overall survival (OS)

    Overall Survival will be analyzed 12 months after the last patient is enrolled. Overall survival will be assessed using a two-sided, log-rank test. The survival function will be estimated using the Kaplan-Meier product limit method. In addition, two-sided 95% confidence intervals for the median overall survival will be computed

    Measured: Up to 12 months

  6. Biomarker response

    Proportion of patients with carcinoembryonic antigen (CEA) response with ≥ 50% decline from baseline (in patients with baseline level ≥ 3.2) post combination therapy with Tas-102 and 90Y radioembolization. Maximum percent change will be calculated. CEA level will only be followed for participants with elevated level (≥3.2) at baseline.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2015 (estimated)
  2. Study start9 Jan 2017
  3. Primary completion20 May 2021
  4. Study completion31 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02602327
Sponsor's protocol ID
16452
Other IDs
NCI-2017-01321
Status last verified
Jul 2022
First submitted
9 Nov 2015
Last updated
1 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Fidelman N, Atreya CE, Griffith M, Milloy MA, Carnevale J, Cinar P, Venook AP, Van Loon K. Phase I prospective trial of TAS-102 (trifluridine and tipiracil) and radioembolization with 90Y resin microspheres for chemo-refractory colorectal liver metastases. BMC Cancer. 2022 Dec 13;22(1):1307. doi: 10.1186/s12885-022-10401-0.

    PubMed 36514060

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tas-102 and SIR-Sphere in people with Colon Cancer and Rectal Cancer, run by University of California, San Francisco at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine dose limiting toxicities (DLT) (time frame: 56 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02602327, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2022.

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