TACE Plus Axitinib and Hydroxychlorquine for Liver-Dominant Metastatic Colorectal Cancer (CRC) (TACE-Ax-HCQ)

April 25, 2024 updated by: Abramson Cancer Center at Penn Medicine

Phase 1B Study of Hepatic Chemoembolization Plus Axitinib and Hydroxychlorquine for Liver-Dominant Metastatic Adenocarcinoma Of The Colon And Rectum

Liver metastases are a leading cause of death among patients with metastatic colorectal cancer. Duration of disease control is short following 2nd-line or later systemic therapy. Liver-directed therapy such as TACE has a higher response rate and improves progression-free survival (PFS), but the benefit is still limited. Cancer cells escape ischemic cell death via autophagy and hypoxia-inducible factor (HIF) activation. We hypothesize that blocking autophagy and the vascular endothelial growth factor (VEGF) pathway will improve both response and PFS following TACE.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Subjects with liver-dominant colorectal cancer metastases failing at least one line of systemic therapy will receive 2 weeks of axitinib 5mg twice daily (BID) and HCQ 600 mg BID followed by lobar or segmental TACE monthly until the entire tumor burden is treated, then continue axitinib/HCQ until progression or intolerable toxicity. Response and hepatic progression-free survival (HPFS) will be assessed one month post-TACE, then every 3 months.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18 years or more.
  2. Pathologically-verified diagnosis of colorectal adenocarcinoma.
  3. Measurable metastasis to liver with at least one dimension ≥ 1.0 cm.
  4. Liver dominant metastases as judged by multidisciplinary team consensus review of cross-sectional imaging of the chest, abdomen and pelvis.
  5. At least 2 weeks must have elapsed from the last dose of chemotherapy before starting HCQ and at least 4 weeks must have elapsed from the last dose of VEGF/VEGFR therapy prior to starting axitinib.
  6. Subjects must be at least 2 weeks beyond prior radiotherapy or surgery, and have recovered from all therapy associated toxicities.
  7. Eastern Cooperative Oncology Group (ECOG) Performance status must be 0-1 (see Appendix II).
  8. Absolute granulocyte count > 1,500/ul, platelet count > 75,000/ul, International Normalized Ratio (INR) < 1.6
  9. Serum creatinine < 2.0 mg/dl; serum bilirubin < 2.0 mg/dl.
  10. Urine protein:creatinine ratio < 1 or 24-hour urine protein < 1 gm/day
  11. Liver function Child-Pugh A
  12. Competent and willing to provide informed consent
  13. Patients of reproductive potential agree to use approved contraceptive methods per section 5.4

Exclusion Criteria:

  1. Contraindications to angiography and selective visceral catheterization:

    1. severe allergy or intolerance to contrast media not controllable with prophylaxis.
    2. bleeding diathesis not correctable by usual forms of therapy.
    3. severe peripheral vascular disease precluding catheterization.

  2. Contraindications to hepatic artery embolization:

    1. high risk of hepatic failure, indicated by the constellation of greater than 50% liver replacement by tumor, lactate dehydrogenase (LDH) >425 mU/ml, aspartate aminotransferase (AST) >100mU/ml. and bilirubin >2 mg/dl.
    2. tumor volume >75% of total liver volume.
    3. portal vein occlusion without hepatopetal collateral flow demonstrated by angiography; or portal hypertension with hepatofugal flow.
    4. hepatic encephalopathy.
  3. Prior hepatic arterial infusion chemotherapy or hepatic radiation therapy. Prior surgical resection or ablation of liver metastases is acceptable.
  4. No more than two prior lines of systemic chemotherapy.
  5. Pregnancy or lactation
  6. Known allergic reactions to irinotecan, HCQ or axitinib
  7. Allergy to contrast not mitigated by usual prophylaxis
  8. Serious infection requiring intravenous therapy.
  9. Known retinal disease
  10. Poorly controlled hypertension, defined as a blood pressure > 150/100 at the time of enrollment. Patients with a preexisting hypertension must be on a stable anti-hypertensive regimen
  11. History of abdominal fistula, gastrointestinal perforation, or serious non-healing wounds, ulcers, or bone fractures
  12. Known New York Heart Association class II or greater congestive heart failure (defined as symptoms of fatigue, dyspnea, or other symptoms with ordinary physical activity)
  13. Known untreated brain metastases. History of treated metastases off steroids allowed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: TACE+axitinib+HCQ
2 weeks of axitinib 5mg BID and hydroxychloroquine 600 mg BID followed by lobar or segmental trans arterial chemoembolization monthly until the entire tumor burden is treated, then continue axitinib/HCQ until progression or intolerable toxicity.
Drug: Axitinib 5 MG
axitinib 5 mg po BID until progression or intolerance
Drug: Hydroxychloroquine Pill
hydroxychloroquine 600 mg po BID until progression or intolerance
Procedure: trans arterial chemoembolization
segmental or lobar TACE at 4-8 week intervals until entire tummy burden is treated.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Serious adverse event (SAE) rate
Time Frame: 12 months
SAE is scored by CTCAE v5 (G3 or higher) and the 2017 revision of the Society of Interventional Radiology (SIR) Complications Classification categories 3-5.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
objective response rate in the liver
Time Frame: 3 months
complete and partial response rate by RECIST and modified RECIST
3 months
Hepatic progression-free survival
Time Frame: 12 months
Time from initiation of therapy to progression in the liver by RECIST, death from any cause, or last documented progression-free status.
12 months
Progression-free survival
Time Frame: 12 months
Time from initiation of therapy to progression anywhere by RECIST, death from any cause, or last documented progression-free status.
12 months
Overall survival
Time Frame: 24 months
Time from initiation of therapy to death or last follow-up alive
24 months
axitinib treatment intensity
Time Frame: 12 months
Weeks on axitinib therapy multiplied by percentage of initially prescribed dose
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Abramson Cancer Center at Penn Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Pfizer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael C Soulen, MD, Abramson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 24, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 25, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 25, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 30, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 5, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UPCC03221

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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