Risk-Based Therapy for Liver Cancer

Recruiting at 220 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Anticoagulants, ACE inhibitors, others

Disqualifiers: Prior chemotherapy, Organ transplant, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

236 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you may need to stop taking some of your current medications. The trial does not allow participants to be on corticosteroids, certain anticonvulsants, specific antibiotics, antifungals, grapefruit juice, St. John's wort, therapeutic anticoagulants, or ACE inhibitors. If you are taking any of these, you will need to stop them before starting the trial.

What data supports the effectiveness of the drugs used in the Risk-Based Therapy for Liver Cancer trial?

Research shows that combinations of drugs like cisplatin, doxorubicin, and 5-fluorouracil have been used in various studies for liver cancer, demonstrating potential benefits in survival and response rates. For example, the PIAF regimen, which includes these drugs, has shown improved response rates and survival in patients with unresectable liver cancer. ^{1 2 3 4 5}

What safety data exists for the treatment options in the clinical trial for liver cancer?

Some of the drugs used in liver cancer treatment, like Cisplatin and Irinotecan, can cause liver and kidney damage. It's important for doctors to carefully manage these treatments, especially in patients with liver problems, to avoid serious side effects. ^{6 7 8 9 10}

What makes the Risk-Based Therapy for Liver Cancer unique?

This treatment is unique because it combines multiple drugs like Cisplatin, Doxorubicin, and others, which are typically used in different cancers, to target liver cancer. This approach may offer a novel way to treat liver cancer by using a combination of drugs that work in different ways, potentially improving effectiveness compared to standard treatments like sorafenib. ^{11 12 13 14 15}

What is the purpose of this trial?

This phase III trial studies the side effects and how well risk-based therapy works in treating younger patients with newly diagnosed liver cancer. Surgery, chemotherapy drugs (cancer fighting medicines), and when necessary, liver transplant, are the main current treatments for hepatoblastoma. The stage of the cancer is one factor used to decide the best treatment. Treating patients according to the risk group they are in may help get rid of the cancer, keep it from coming back, and decrease the side effects of chemotherapy.

Research Team

Howard M Katzenstein

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for young patients with newly diagnosed liver cancer called hepatoblastoma. They must not have had any previous chemotherapy or other treatments for the condition, and their organ functions should meet specific criteria. Pregnant or breastfeeding females are ineligible, as well as those on certain medications like corticosteroids or anticoagulants.

Inclusion Criteria

In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy

Various laboratory and imaging criteria must be met

All patients and/or their parents or legal guardians must sign a written informed consent

Exclusion Criteria

My early-stage cancer tissue wasn't reviewed within 2 weeks after surgery.

I have not had chemotherapy, other cancer drugs, or experimental treatments recently.

I have not had an organ transplant, am not pregnant or breastfeeding, and do not have an uncontrolled infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive risk-based therapy including surgery, chemotherapy, and potentially liver transplant based on risk group

Up to 1 year

Multiple visits for chemotherapy cycles and surgical procedures

Follow-up

Participants are monitored for safety and effectiveness after treatment

At least 4 years

Treatment Details

Interventions

• Cisplatin
• Doxorubicin Hydrochloride
• Fluorouracil
• Irinotecan Hydrochloride
• Liver Transplantation
• Temsirolimus
• Therapeutic Conventional Surgery
• Vincristine Sulfate

Trial Overview The study tests risk-based therapy involving surgery, various chemotherapy drugs (Dexrazoxane, Vincristine Sulfate, Fluorouracil, etc.), and potentially a liver transplant based on the stage of cancer. The aim is to see if tailoring treatment by risk group can effectively treat the cancer while minimizing side effects.

Participant Groups

Group I: Very low-risk group Experimental Treatment 2 Interventions

Patients undergo surgery and then receive no further treatment.

Group II: Low-risk group (regimen T) Experimental Treatment 5 Interventions

Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Group III: Intermediate-risk group (regimen F) Experimental Treatment 8 Interventions

Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Group IV: High-risk group (regimen W) Experimental Treatment 7 Interventions

(regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

Group V: High-risk group (regimen H) Experimental Treatment 9 Interventions

Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup analysis of the EACH study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon-alpha, doxorubicin and 5-fluorouracil chemotherapy. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Modified cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability, and survival of initially unresectable hepatocellular carcinoma. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Gender difference in Cisplatin-induced nephrotoxicity in a rat model: greater intensity of damage in male than female. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Hepatotoxicity of chemotherapy. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Management of hepatotoxicity of chemotherapy and targeted agents. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Integrating irinotecan in standard chemotherapy: A novel dose-density combination for high-risk pediatric sarcomas. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy dosing in the setting of liver dysfunction. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Sorafenib for Hepatocellular Carcinoma Refractory to Transarterial Chemoembolization: Retrospective Subgroup Analysis of 2 Prospective Trials. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Feasibility of oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX-4) in cirrhotic or liver transplant patients: experience in a cohort of advanced hepatocellular carcinoma patients. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of anticancer agents in patients with impaired liver function. [2019]

15. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of combination chemotherapy with capecitabine plus cisplatin in patients with unresectable hepatocellular carcinoma. [2015]