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Sorafenib + mFOLFOX for Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01775501
Recruitment Status : Completed
First Posted : January 25, 2013
Results First Posted : April 22, 2020
Last Update Posted : April 22, 2020
Information provided by (Responsible Party):
Goyal, Lipika, Massachusetts General Hospital

Brief Summary:

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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer
Drug Information available for: Sorafenib

Arm Intervention/treatment
Experimental: Experimental Treatment Arm
FOLFOX (Leucovorin, Fluorouracil and Oxaliplatin) + Sorafenib Sorafenib: orally, twice daily FOLFOX: injected via portacath once every two weeks
Drug: Leucovorin
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

Drug: Fluorouracil
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

Drug: Oxaliplatin
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

Drug: Sorafenib
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

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. Median Overall Survival [ Time Frame: From registration until death, median duration of 15.1 months ]
    The duration of time from study registration until death.

  5. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed advanced HCC
  • Barcelona Clinic Liver Cancer stage C or stage B if you cannot tolerate or failed TACE
  • No cirrhosis or Child-Pugh A cirrhosis
  • Measurable lesions
  • All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 grade 1 or less
  • Able to swallow and retain oral medication

Exclusion Criteria:

  • Prior systemic regimens for HCC
  • Uncontrolled hypertension
  • CLIP score > 3
  • ECOG PS > 1
  • Clinically apparent central nervous system metastases or carcinomatous meningitis
  • Pregnant or breastfeeding
  • Active or clinically significant cardiac disease
  • Evidence or history of bleeding diathesis or coagulopathy
  • Any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 2 or higher within 4 weeks of enrollment
  • Presence of a non-healing wound, non-healing ulcer, or bone fracture
  • History of organ allograft
  • Any malabsorption condition
  • Medical or psychiatric condition that constitutes an unacceptable risk for participation in this trial
  • Have received another investigational agent within 4 weeks of first dose of sorafenib
  • Previously untreated or concurrent cancer except those treated more than 3 years ago
  • History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
  • QTC>500msec or history of uncontrolled angina, arrhythmias, or congestive heart failure
  • Concurrent systemic and local anti-cancer therapy
  • Prior use of sorafenib, oxaliplatin or 5FU
  • Major surgery within 30 days
  • Concurrent use of aspirin>100mg
  • Therapeutic anticoagulation with vitamin K antagonists or with heparins or heparinoids

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01775501

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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
Sponsors and Collaborators
Massachusetts General Hospital
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Principal Investigator: Lipika Goyal, MD MGH
  Study Documents (Full-Text)

Documents provided by Goyal, Lipika, Massachusetts General Hospital:
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Responsible Party: Goyal, Lipika, Prinicipal Investigator, Massachusetts General Hospital Identifier: NCT01775501    
Other Study ID Numbers: 12-218
First Posted: January 25, 2013    Key Record Dates
Results First Posted: April 22, 2020
Last Update Posted: April 22, 2020
Last Verified: April 2020
Keywords provided by Goyal, Lipika, Massachusetts General Hospital:
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents
Vitamin B Complex
Protein Kinase Inhibitors
Enzyme Inhibitors