Overview
TACE Plus Axitinib and Hydroxychlorquine for Liver-Dominant Metastatic Colorectal Cancer (CRC)
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2023-11-01
2023-11-01
Target enrollment:
0
0
Participant gender:
All
All
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.Phase:
Phase 1Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Abramson Cancer Center of the University of PennsylvaniaCollaborator:
PfizerTreatments:
Axitinib
Hydroxychloroquine
Criteria
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.