NCI Community Oncology Research Program - Protocol Summary
RTOG 1112 - "RANDOMIZED PHASE III STUDY OF SORAFENIB VERSUS STEREOTACTIC BODY RADIATION THERAPY FOLLOWED BY SORAFENIB IN HEPATOCELLULAR CARCINOMA"
The summary below serves as a brief review of the treatment plan and eligibility for the protocol.
This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
Please follow the "Full Protocol" link or contact NCORP-KC for complete protocol information.
GI Clinical Trial
CANCER TYPE: Liver
RESEARCH BASE: NRG
NCT NUMBER: NCT01730937
HIPPA FORM: DOWNLOAD HIPPA FORM
Consent Form: VIEW CONSENT FORM
HCC, BCLC stage Intermediate (B) or advanced (C), Sorafenib alone VS. SBRT + Sorafenib. DCP-001 Eligible
Treatment Plan (Provided drug: none)
Day 1-Start Sorafenib 400mg BID daily (Dose level 0). Each cycle=28 continuous days until progression, toxicity or 5 years
SBRT delivered over 5 fractions delivered over 5-15 days. The prescription dose may be 50 Gy, 45 Gy, 40 Gy, 35 Gy, 30 Gy or 27.5 Gy in 5 fractions, based on normal tissue constraints.
Sorafenib to start Day 1-5 post SBRT completion at 200mg BID (level -1). Each cycle=28 days until progression, toxicity or 5 years
Sorafenib will be increased to 400mg BID during cycle #2 if clinically appropriate, as per Section 7.1.1.
- Patients must have an HCC diagnosis (initial, recurrent, progressive and/or refractory to other therapies) by at least one criterion listed below ≤360 days prior to study entry
- Pathologically (histologically or cytologically) proven diagnosis of HCC.
- At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multi-phasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis.
- For patients whose CURRENT disease is vascular only:
Enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI, in a patient with known HCC (diagnosed previously < 720 days)
- Measureable hepatic disease and/or presence of vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) which may not be measureable as per RECIST, as defined in Section 11.0) on liver CT or MRI, within 28 days of registration
- Appropriate for protocol entry based upon the following minimum diagnostic workup:
- History/physical examination including examination for encephalopathy, ascites, weight, height, and blood pressure within 14 days prior to study entry
- Assessment by radiation oncologist and medical oncologist or hepatologist who specializes in treatment of HCC within 28 days prior to study entry
- Pre-randomization Scan (REQUIRED for All Patients): CT scan chest/abdomen/pelvis with multiphasic liver CT or multiphasic liver MR scan within 28 days prior to study entry. MRI of abdomen with contrast and pelvis is permitted. See Appendix V and Section 4.1.7 for details.
- Zubrod Performance Status 0-2 within 28 days prior to study entry
- Age ≥ 18
- All blood work obtained within 14 days prior to study entry with adequate organ marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
- Platelets ≥ 70,000 cells/mm3
- Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
- Total bilirubin < 2 mg/dL
- Internationalized Normal Ratio (INR) < 1.7
- Albumin ≥ 28 g/L
- AST and ALT < 6 times ULN
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min
- BCLC stage: Intermediate (B) or advanced (C) within 14 days prior to study entry
- Child-Pugh score A within 14 days prior to study entry
- Women of childbearing potential and male participants must agree to practice adequate contraception while on study and for at least 6 months following the last dose of RT and for at least 28 days following the last dose of sorafenib (whichever is later).
- Unsuitable for resection or transplant or radiofrequency ablation (RFA)
- Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) or drug eluting beads (DEB) for any of the following reasons, as described by Raoul et al (2011):
- Technical contraindications: arteriovenous fistula, including surgical portosystemic shunt or spontaneous portosystemic shunt
- Severe reduction in portal vein flow: due to tumor portal vein, IVC or atrial invasion or bland portal vein occlusion
- Medical contraindications including congestive heart failure, angina, severe peripheral vascular disease
- Presence of extrahepatic disease
- No response post TACE (or DEB) or progressive HCC despite TACE. Prior TACE or DEB is allowed but must be > 28 days from study entry
- Serious toxicity following prior TACE (or DEB). Prior TACE or DEB must be > 28 days from study entry
- Other medical comorbidities making TACE (or DEB) unsafe and/or risky (e.g. combination of relative contraindications including age > 80 years, tumor > 10 cm, > 50% replacement of the liver by HCC, extensive multinodular bilobar HCC, biliary drainage)
- Patients treated with prior surgery are eligible for this study if they otherwise meet eligibility criteria.
- Patient must be able to provide study-specific informed consent prior to study entry.
- No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (Note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
- No prior sorafenib use > 60 days. Note that prior chemotherapy for HCC or a different cancer is allowable. See Section 3.2.1.
- No prior radiotherapy to the region of the liver that would result in excessive doses to normal tissues due to overlap of radiation therapy fields
- No prior selective internal radiotherapy/hepatic arterial Yttrium therapy, at any time
- No severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months before registration
- Transmural myocardial infarction within the last 6 months prior to study entry
- Unstable ventricular arrhythmia within the last 6 months prior to study entry
- Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry
- Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 60 days prior to study entry
- Bleeding within 60 days prior to study entry due to any cause, requiring transfusion
- Thrombolytic therapy within 28 days prior to study entry. Subcutaneous heparin is permitted.
- Known bleeding or clotting disorder
- Uncontrolled psychotic disorder
- No pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
- No hepatocellular carcinoma > 15 cm
- Total maximal sum of hepatocellular carcinomas or a single conglomerate HCC cannot be greater than 20 cm
- Cannot have more than 5 discrete intrahepatic parenchymal foci of HCC
- No direct tumor extension into the stomach, duodenum, small bowel or large bowel
- No measureable common or main branch biliary duct involvement with HCC
- No extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 3.0cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions). Note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm.
- No use of regular phenytoin, carbamzepine, hypericum perforatum [also known as St. John’s wort] or rifampin
- No use of combination anti-retroviral therapy for HIV, as these agents may modulate cytochrome P450 isozymes
- No prior liver transplant