Second Line Therapy for Advanced Intrahepatic Cholangiocarcinoma
Study Details
Study Description
Brief Summary
This is a prospective, Two-arm, comparative, randomized, controlled phase II trial, to explore the efficacy and safety of Regorafenib and HAIC vs. FOLFOX as Second Line Therapy for Advanced Intrahepatic Cholangiocarcinoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Currently, complete surgical resection represents the only potentially curative treatment option for cholangiocarcinoma (CCA, including intrahepatic, hilar and distal CCA) and gallbladder carcinoma (GBCA). However,only less than 25% of patients are resectable at diagnosis and, even in this subset of patients, relapse rate is high.
Cisplatin and gemcitabine combination was identified as the standard first-line chemotherapy, yielding a median progression free survival (PFS) and median OS of 8.5 and 11.7 months, respectively. FOLFOX was the standard second-line chemotherapy. But the benefit of FOLFOX was limited.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Regorafenib and HAIC Regorafenib HAIC with FOLFOX |
Drug: Regorafenib and HAIC
Regorafenib: oral 80mg/day, D1-21, Q28d; HAIC with FOLFOX: hepatic artery infusion Oxa 85 mg/m2, CF 400 mg/m2, 5-Fu 400 mg/m2, 5-Fu 2400mg/m2 infusion 48h.
|
| Active Comparator: FOLFOX FOLFOX |
Drug: FOLFOX
Oxa 85 mg/m2, CF 400 mg/m2, 5-Fu 400 mg/m2, 5-Fu 2400mg/m2 infusion 48h.
|
Outcome Measures
Primary Outcome Measures
- Objective response rate (ORR) [12month]
the rate of complete response and partial response among all evaluable patients
Secondary Outcome Measures
- Disease control rate (DCR) [12 months]
the rate of complete response, partial response and stable disease among all evaluable patients
- Progression-free Survival (PFS) [12 months]
A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause.
- Overall Survival (OS) [24 months]
Duration from the date of initial treatment to the date of death due to any cause.
- Adverse events (AE) [24 months]
Adverse events in each cycle were documented based on CTCAE v 4.03
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed and dated IRB/IEC-approved Informed Consent.
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Cytological or histological diagnosis of locally advanced or metastatic adenocarcinoma of the Intrahepatic Cholangiocarcinoma.
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Disease progressing after first-line chemotherapy with gemcitabine and platinum analogs (only one prior systemic therapy allowed).
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Age 18-75 years
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Karnofsky Performance Status > 50%
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Estimated life expectancy of at least 3 months.
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Negative pregnancy test (if female in reproductive years).
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Adequate bone marrow, liver and kidney function: leukocyte > 3500/mm3; absolute neutrophil count (ANC) > 1500/mm3; platelet count > 100000/mm3; hemoglobin > 10 g/dl; creatinine < 1.5 mg/dL; total bilirubin ≤ 1.5 x upper limit of normal range (ULN); SGOT e SGPT ≤ 2.5 ULN
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At the time of start of treatment, at least 2 weeks must have elapsed since completion of prior chemotherapy, minor surgery and radiotherapy (provided that no more than 25% of bone marrow reserve has been irradiated).
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Resolution of all acute toxic effects of any prior chemotherapy, surgery or radiotherapy to NCI CTC (Version 4.03) grade ≤ 1 for hematologic toxicities and ≤ 2 for non hematologic toxicities, with the exception of alopecia.
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Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol.
Exclusion Criteria:
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History of cardiac disease
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Ongoing infection > Grade 2 according to NCI-CTCAE version 4.03. Hepatitis B is allowed if no active replication (defined as abnormal ALT >2xULN associated with HBV DNA >20,000 IU/mL) is present
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Severe co-morbid illness and/or active infections including active hepatitis C and human immunodeficiency virus (HIV) infection
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History of interstitial lung disease (ILD).
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Any cancer curatively treated < 3 years prior to study entry, except cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Staging: Ta, Tis and T1).
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Renal failure requiring hemo- or peritoneal dialysis.
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Clinically significant GI bleeding (CTCAE 4.03 grade 3 or higher) within 30 days prior to start of screening
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Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months prior to start of screening.
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History of organ allograft, cornea transplantation will be allowed
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Active CNS metastases not controllable with radiotherapy or corticosteroids Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR.
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Known history of hypersensitivity to study drugs
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Non-healing wound, ulcer, or bone fracture.
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Patients with seizure disorder requiring medication.
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Acute steroid therapy or taper for any purpose (chronic steroid therapy is acceptable provided that the dose is stable for 1 month before start of screening and thereafter).
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Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
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Pregnant or lactating women. Women of childbearing potential not employing adequate contraception. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of study treatment and a negative result must be documented before first dose of study drug.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tianjin Medical University Cancer Institute and Hospital | Tianjin | China | 300060 |
Sponsors and Collaborators
- Tianjin Medical University Cancer Institute and Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E20220698