Sorafenib + mFOLFOX for Hepatocellular Carcinoma

NCT01775501 | Completed Phase 2 Results DMC

• 1 other identifier: 12-218
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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.

Conditions

Hepatocellular Cancer

Keywords

sorafenib; FOLFOX

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  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).

  The amount of time from registration until disease progression or death, median duration 7.7 months

Secondary Outcomes (5)

• Number of Patients Experiencing Adverse Events

  From the start of treatment until 30 days after the end of treatment, median duration of 10.7 months

• Overall Response Rate

  2 years

• Median Progression Free Survival

  From the start of treatment until disease progression or death, median duration of 232 days

• Median Overall Survival

  From registration until death, median duration of 15.1 months

• Duration of Response

  From the time of treatment response until death or disease progression (median duration 172 days)

Study Arms (1)

Experimental Treatment Arm

EXPERIMENTAL

FOLFOX (Leucovorin, Fluorouracil and Oxaliplatin) + Sorafenib Sorafenib: orally, twice daily FOLFOX: injected via portacath once every two weeks

Drug: Leucovorin; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Sorafenib

Interventions

Leucovorin DRUG

200mg/m2 administered IV on Days 1 and 15 of a 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Also known as: Folinic acid

Experimental Treatment Arm

Fluorouracil DRUG

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.

Also known as: 5-FU

Experimental Treatment Arm

Oxaliplatin DRUG

85 mg/m2 IV on Days 1 and 15 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Also known as: Eloxatin

Experimental Treatment Arm

Sorafenib DRUG

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.

Also known as: Nexavar

Experimental Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02125, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Leucovorin; Fluorouracil; Oxaliplatin; Sorafenib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Results Point of Contact

• Title: Dr. Lipika Goyal
• Organization: Massachusetts General Hospital

LGOYAL@PARTNERS.ORG

617-724-4000

Study Officials

• Lipika Goyal, MD

  MGH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: January 18, 2013
• First Posted: January 25, 2013
• Study Start: January 1, 2013
• Primary Completion: July 1, 2018
• Study Completion: December 1, 2019
• Last Updated: April 22, 2020
• Results First Posted: April 22, 2020

Record last verified: 2020-04

Locations

US (3)