Colorectal Neoplasms MalignantPhase 1TACE-Ax-HCQNCT04873895
TACE Plus Axitinib and Hydroxychlorquine for Liver-Dominant Metastatic Colorectal Cancer (CRC)
A Phase 1 study testing Axitinib 5 MG, Hydroxychloroquine Pill and trans arterial chemoembolization in people with Colorectal Neoplasms Malignant, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms Malignant
- What is being tested?
- Axitinib 5 MG, Hydroxychloroquine Pill and trans arterial chemoembolization
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2022to 25 Apr 2024
- 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
- Age 18 years or more.
- Pathologically-verified diagnosis of colorectal adenocarcinoma.
- Measurable metastasis to liver with at least one dimension ≥ 1.0 cm.
- Liver dominant metastases as judged by multidisciplinary team consensus review of cross-sectional imaging of the chest, abdomen and pelvis.
- 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.
- Subjects must be at least 2 weeks beyond prior radiotherapy or surgery, and have recovered from all therapy associated toxicities.
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- Eastern Cooperative Oncology Group (ECOG) Performance status must be 0-1 (see Appendix II).
- Absolute granulocyte count > 1,500/ul, platelet count > 75,000/ul, International Normalized Ratio (INR) < 1.6
- Serum creatinine < 2.0 mg/dl; serum bilirubin < 2.0 mg/dl.
- Urine protein:creatinine ratio < 1 or 24-hour urine protein < 1 gm/day
- Liver function Child-Pugh A
- Competent and willing to provide informed consent
- Patients of reproductive potential agree to use approved contraceptive methods per section 5.4
Who cannot join
- Contraindications to angiography and selective visceral catheterization:
- severe allergy or intolerance to contrast media not controllable with prophylaxis.
- bleeding diathesis not correctable by usual forms of therapy.
- severe peripheral vascular disease precluding catheterization.
- Contraindications to hepatic artery embolization:
- 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.
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- tumor volume >75% of total liver volume.
- portal vein occlusion without hepatopetal collateral flow demonstrated by angiography; or portal hypertension with hepatofugal flow.
- hepatic encephalopathy.
- Prior hepatic arterial infusion chemotherapy or hepatic radiation therapy. Prior surgical resection or ablation of liver metastases is acceptable.
- No more than two prior lines of systemic chemotherapy.
- Pregnancy or lactation
- Known allergic reactions to irinotecan, HCQ or axitinib
- Allergy to contrast not mitigated by usual prophylaxis
- Serious infection requiring intravenous therapy.
- Known retinal disease
- 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
- History of abdominal fistula, gastrointestinal perforation, or serious non-healing wounds, ulcers, or bone fractures
- 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)
- Known untreated brain metastases. History of treated metastases off steroids allowed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
Read the 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.
- Conditions
- Colorectal Neoplasms Malignant
- Being tested
- Axitinib 5 MG, Hydroxychloroquine Pill, trans arterial chemoembolization
- Keywords
- colorectal cancer, liver metastases
- Medical subject headings
- Colonic Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Axitinib 5 MGDrug
axitinib 5 mg po BID until progression or intolerance
Hydroxychloroquine PillDrug
hydroxychloroquine 600 mg po BID until progression or intolerance
trans arterial chemoembolizationProcedure or surgery
segmental or lobar TACE at 4-8 week intervals until entire tummy burden is treated.
| Study group | Role | What they receive |
|---|---|---|
| TACE+axitinib+HCQ | Experimental | 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. Receives: Drug: Axitinib 5 MG; Drug: Hydroxychloroquine Pill; Procedure: trans arterial chemoembolization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious adverse event (SAE) rate
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.
Measured: 12 months
Secondary outcomes (5)
objective response rate in the liver
complete and partial response rate by RECIST and modified RECIST
Measured: 3 months
Hepatic progression-free survival
Time from initiation of therapy to progression in the liver by RECIST, death from any cause, or last documented progression-free status.
Measured: 12 months
Progression-free survival
Time from initiation of therapy to progression anywhere by RECIST, death from any cause, or last documented progression-free status.
Measured: 12 months
Overall survival
Time from initiation of therapy to death or last follow-up alive
Measured: 24 months
axitinib treatment intensity
Weeks on axitinib therapy multiplied by percentage of initially prescribed dose
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2021
- Study start24 Jan 2022
- Primary completion25 Apr 2024
- Study completion25 Apr 2024
Why it stopped: failure to accrue
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Colorectal Neoplasms MalignantStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- single-center open-label Phase 1B trial
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Michael C Soulen, MD, Principal investigator, Abramson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04873895
- Sponsor's protocol ID
- UPCC03221
- Acronym
- TACE-Ax-HCQ
- Status last verified
- Apr 2024
- First submitted
- 30 Apr 2021
- Last updated
- 26 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Fiorentini G, Sarti D, Nani R, Aliberti C, Fiorentini C, Guadagni S. Updates of colorectal cancer liver metastases therapy: review on DEBIRI. Hepat Oncol. 2020 Jan 21;7(1):HEP16. doi: 10.2217/hep-2019-0010.
PubMed 32273974Gade TPF, Tucker E, Nakazawa MS, Hunt SJ, Wong W, Krock B, Weber CN, Nadolski GJ, Clark TWI, Soulen MC, Furth EE, Winkler JD, Amaravadi RK, Simon MC. Ischemia Induces Quiescence and Autophagy Dependence in Hepatocellular Carcinoma. Radiology. 2017 Jun;283(3):702-710. doi: 10.1148/radiol.2017160728. Epub 2017 Mar 2.
PubMed 28253108Fiorentini G, Sarti D, Nardella M, Inchingolo R, Nestola M, Rebonato A, Guadagni S. Chemoembolization Alone or Associated With Bevacizumab for Therapy of Colorectal Cancer Metastases: Preliminary Results of a Randomized Study. In Vivo. 2020 Mar-Apr;34(2):683-686. doi: 10.21873/invivo.11824.
PubMed 32111770Chan SL, Yeo W, Mo F, Chan AWH, Koh J, Li L, Hui EP, Chong CCN, Lai PBS, Mok TSK, Yu SCH. A phase 2 study of the efficacy and biomarker on the combination of transarterial chemoembolization and axitinib in the treatment of inoperable hepatocellular carcinoma. Cancer. 2017 Oct 15;123(20):3977-3985. doi: 10.1002/cncr.30825. Epub 2017 Jun 22.
PubMed 28640364
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1B Study of Hepatic Chemoembolization Plus Axitinib and Hydroxychlorquine for Liver-Dominant Metastatic Adenocarcinoma Of The Colon And Rectum
- ClinicalTrials.gov ID
- NCT04873895
- Acronym / sponsor ID
- TACE-Ax-HCQ / UPCC03221
- Conditions
- Colorectal Neoplasms Malignant
- Keywords
- colorectal cancer, liver metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: failure to accrue
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 24 Jan 2022 (actual)
- Primary completion
- 25 Apr 2024 (actual)
- Study completion
- 25 Apr 2024 (actual)
- First posted
- 5 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single-center open-label Phase 1B trial
| Arm | Type | Receives |
|---|---|---|
| TACE+axitinib+HCQ | Experimental | Drug: Axitinib 5 MG, Drug: Hydroxychloroquine Pill, Procedure: trans arterial chemoembolization2 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age 18 years or more.
- Pathologically-verified diagnosis of colorectal adenocarcinoma.
- Measurable metastasis to liver with at least one dimension ≥ 1.0 cm.
- Liver dominant metastases as judged by multidisciplinary team consensus review of cross-sectional imaging of the chest, abdomen and pelvis.
- 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.
Key exclusion criteria (20 listed)
- Contraindications to angiography and selective visceral catheterization:
- Contraindications to hepatic artery embolization:
- Prior hepatic arterial infusion chemotherapy or hepatic radiation therapy. Prior surgical resection or ablation of liver metastases is acceptable.
- No more than two prior lines of systemic chemotherapy.
- Pregnancy or lactation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Axitinib 5 MGaxitinib 5 mg po BID until progression or intolerance | Drug | TACE+axitinib+HCQ |
| Hydroxychloroquine Pillhydroxychloroquine 600 mg po BID until progression or intolerance | Drug | TACE+axitinib+HCQ |
| trans arterial chemoembolizationsegmental or lobar TACE at 4-8 week intervals until entire tummy burden is treated. | Procedure or surgery | TACE+axitinib+HCQ |
Primary outcome
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.
5 secondary outcomes
objective response rate in the liver
Time frame: 3 months
Hepatic progression-free survival
Time frame: 12 months
Progression-free survival
Time frame: 12 months
Overall survival
Time frame: 24 months
axitinib treatment intensity
Time frame: 12 months
Results and safety
The study was stopped early (reason given: failure to accrue). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2024.
- Background: PubMed 32273974Fiorentini G, Sarti D, Nani R, Aliberti C, Fiorentini C, Guadagni S. Updates of colorectal cancer liver metastases therapy: review on DEBIRI. Hepat Oncol. 2020 Jan 21;7(1):HEP16. doi: 10.2217/hep-2019-0010.
- Background: PubMed 28253108Gade TPF, Tucker E, Nakazawa MS, Hunt SJ, Wong W, Krock B, Weber CN, Nadolski GJ, Clark TWI, Soulen MC, Furth EE, Winkler JD, Amaravadi RK, Simon MC. Ischemia Induces Quiescence and Autophagy Dependence in Hepatocellular Carcinoma. Radiology. 2017 Jun;283(3):702-710. doi: 10.1148/radiol.2017160728. Epub 2017 Mar 2.
- Background: PubMed 32111770Fiorentini G, Sarti D, Nardella M, Inchingolo R, Nestola M, Rebonato A, Guadagni S. Chemoembolization Alone or Associated With Bevacizumab for Therapy of Colorectal Cancer Metastases: Preliminary Results of a Randomized Study. In Vivo. 2020 Mar-Apr;34(2):683-686. doi: 10.21873/invivo.11824.
- Background: PubMed 28640364Chan SL, Yeo W, Mo F, Chan AWH, Koh J, Li L, Hui EP, Chong CCN, Lai PBS, Mok TSK, Yu SCH. A phase 2 study of the efficacy and biomarker on the combination of transarterial chemoembolization and axitinib in the treatment of inoperable hepatocellular carcinoma. Cancer. 2017 Oct 15;123(20):3977-3985. doi: 10.1002/cncr.30825. Epub 2017 Jun 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael C Soulen, MD principal investigator
Abramson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Axitinib 5 MG, Hydroxychloroquine Pill and trans arterial chemoembolization in people with Colorectal Neoplasms Malignant, run by Abramson Cancer Center at Penn Medicine 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 13 inclusion and 20 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: stopped early, as of the sponsor's last update on 26 Apr 2024. 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 was stopped early (reason given: failure to accrue). Results are not available in the source record.
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?
Serious adverse event (SAE) rate (time frame: 12 months). 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 NCT04873895, which also lists 4 linked publications.
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 26 Apr 2024.