Status:
TERMINATED
TACE Plus Axitinib and Hydroxychlorquine for Liver-Dominant Metastatic Colorectal Cancer (CRC)
Lead Sponsor:
Abramson Cancer Center at Penn Medicine
Collaborating Sponsors:
Pfizer
Conditions:
Colorectal Neoplasms Malignant
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief 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 therap...
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 s...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
January 24 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 25 2024
Estimated Enrollment :
5 Patients enrolled
Trial Details
Trial ID
NCT04873895
Start Date
January 24 2022
End Date
April 25 2024
Last Update
April 26 2024
Active Locations (1)
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1
Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104