Sorafenib + mFOLFOX for Hepatocellular Carcinoma
|ClinicalTrials.gov Identifier: NCT01775501|
Recruitment Status : Completed
First Posted : January 25, 2013
Results First Posted : April 22, 2020
Last Update Posted : April 22, 2020
This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational combination of drugs to learn whether the drug combination works in treating a specific cancer. "Investigational" means that the modified FOLFOX and sorafenib combination is still being studied and that research doctors are trying find out more about it-such as the safest dose to use, the side effects it may cause, and if the combination is effective for treating different types of cancer. It also means that the FDA has not yet approved the modified FOLFOX and sorafenib combination that will be used in this study for liver cancer.
FOLFOX is a combination of three drugs: folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin. The dosage amounts for some of these FDA approved drugs will be modified slightly in this study. The FOLFOX combination is approved by the FDA and is a standard treatment of colorectal cancer. However, it is not approved for the treatment of liver cancer.
Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of liver cancer. It is also currently being tested in various other cancers. Sorafenib works by slowing down and/or stopping the development of new cancer cells and new blood vessels. By slowing down and/or stopping the growth of new blood vessels around a tumor, it is believed that sorafenib prevents or slows down the growth of tumors.
In this research study, sorafenib, the standard treatment, is being combined with modified FOLFOX, which has shown some antitumor activity in liver cancer.
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Cancer||Drug: Leucovorin Drug: Fluorouracil Drug: Oxaliplatin Drug: Sorafenib||Phase 2|
After agreeing to participate in this study, the patient will be asked to undergo some screening tests or procedures to find out if he/she is eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that the patient does not take part in the research study. If the patient has had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history, physical exam, performance status, electrocardiogram, assessment of tumor, blood tests, urine test, pregnancy test and optional research biopsy. If these tests show that the patient is eligible to participate in the research study, he/she will begin the study treatment. If the patient does not meet the eligibility criteria, he/she will not be able to participate.
If the patient takes part in this research study, he/she will be given a sorafenib study drug-dosing diary for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks), during which time the patient will be taking the study drug twice daily. The diary will also include special instructions for sorafenib.
There will be a 2-week Lead-in period, in which the patient will receive sorafenib alone for the first two weeks of the study. Cycle 1 will begin once the patient receives the combination sorafenib and FOLFOX.
For FOLFOX, all three chemotherapy drugs will be injected through a central vein in the patient's chest (portacath) and will be given once every two weeks (14 days), starting on Day 15 of Cycle 1. The patient will receive oxaliplatin first as a 2-hour infusion, followed by leucovorin, and then 5-FU. The 5-FU infusion can last up to 46 hours and will be given through a small portable pump. The investigator will ask the patient to come back to the clinic on day 3 (46 hours after begin 5-FU dose) for pump discontinuance.
During all cycles the patient will have a physical exam and the patient will be asked questions about his/her general health and specific questions about any problems that he/she might be having and any medication he/she may be taking.
As part of the research study the patient will undergo research blood tests that will measure certain proteins in the blood to learn what affect the study treatment may have on you and your disease. About 1 teaspoon of blood will be drawn on Days 3 and 14 during your first two weeks of sorafenib alone, again on Days 14 and 28 post-treatment with FOLFOX-sorafenib and, if available, at the time of progression (if the patient's disease gets worse).
The patient's blood pressure will be monitored once every week for the first 6 weeks of the study (once a week during sorafenib lead-in period and Cycle 1). The investigator will asses the patient's tumor by chest, abdominal and pelvic CT or MRI scan once every 8 weeks throughout the study.
After the final dose of the study drug the investigator will ask the patient to come back to the clinic to repeat the following procedures: medical review, physical examination, blood tests, pregnancy test and tumor assessment by CT or MRI. The investigator would like to keep track of patient's medical condition for the rest of his/her life. The investigator would like to do this by calling the patient on the telephone once a year to see how the patient is doing. Keeping in touch with the patient and checking his/her condition every year helps the investigator look at the long-term effects of the research study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Sorafenib in Combination With Modified FOLFOX in Patients With Advanced Hepatocellular Carcinoma|
|Actual Study Start Date :||January 2013|
|Actual Primary Completion Date :||July 2018|
|Actual Study Completion Date :||December 2019|
Experimental: Experimental Treatment Arm
FOLFOX (Leucovorin, Fluorouracil and Oxaliplatin) + Sorafenib Sorafenib: orally, twice daily FOLFOX: injected via portacath once every two weeks
200mg/m2 administered IV on Days 1 and 15 of a 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Other Name: Folinic acid
5-FU continuous infusion: 2400mg/m2 total (1200mg/m2/d on day 1 and 2) to start on Day 1 and Day 15 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Other Name: 5-FU
85 mg/m2 IV on Days 1 and 15 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Other Name: Eloxatin
400mg po BID continuously for a 2 week lead-in phase and then Days 1-28 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Other Name: Nexavar
- Time to Progression [ Time Frame: The amount of time from registration until disease progression or death, median duration 7.7 months ]
The median amount of time from the time of registration until disease progression. Disease progression was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
- Number of Patients Experiencing Adverse Events [ Time Frame: From the start of treatment until 30 days after the end of treatment, median duration of 10.7 months ]To evaluate the tolerability and toxicities of FOLFOX-S regimen in this population of patients.
- Overall Response Rate [ Time Frame: 2 years ]
Overall response rate is the number of participants that achieved either a complete or partial response according to RECIST 1.1 criteria.
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
- Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Median Progression Free Survival [ Time Frame: From the start of treatment until disease progression or death, median duration of 232 days ]The median duration of time from the start of treatment until disease progression or death
- Median Overall Survival [ Time Frame: From registration until death, median duration of 15.1 months ]The duration of time from study registration until death.
- Duration of Response [ Time Frame: From the time of treatment response until death or disease progression (median duration 172 days) ]The median amount of time from achieving a response (partial or complete) until disease progression, death, or loss to follow-up.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01775501
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02115|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02125|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Lipika Goyal, MD||MGH|