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

  • STATUS
    Recruiting
  • End date
    Dec 11, 2023
  • participants needed
    25
  • sponsor
    Abramson Cancer Center of the University of Pennsylvania
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Updated on 11 May 2022
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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. 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.

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.

Details
Condition Colorectal Neoplasms Malignant
Treatment Hydroxychloroquine Pill, Axitinib 5 MG, trans arterial chemoembolization
Clinical Study IdentifierNCT04873895
SponsorAbramson Cancer Center of the University of Pennsylvania
Last Modified on11 May 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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
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
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