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

Stopped early · Phase 1

Conditions studied: Colorectal Neoplasms Malignant

In brief

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.

Key facts

Study ID: NCT04873895
Run by: Abramson Cancer Center at Penn Medicine
People needed: 5
Starts: 2022-01-24
Expected to finish: 2024-04-25
Last updated by the study team: 2024-04-26

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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.

Where it is running

Abramson Cancer Center — Philadelphia, Pennsylvania, United States

Full record on ClinicalTrials.gov

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