Risk-Based Therapy for Liver Cancer

Not currently recruiting at 235 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of different treatments for young patients newly diagnosed with liver cancer, specifically hepatoblastoma. It aims to identify the best treatment based on the cancer's risk stage, which may help eliminate the cancer, prevent recurrence, and reduce chemotherapy side effects. The trial includes various treatment methods such as surgery, chemotherapy drugs (including Cisplatin, Doxorubicin Hydrochloride, Fluorouracil, Irinotecan Hydrochloride, Temsirolimus, and Vincristine Sulfate), and potentially liver transplants, depending on the cancer's risk category. It seeks patients who are newly diagnosed with hepatoblastoma and have not yet started any other treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients early access to potentially effective treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the chemotherapy treatments in this trial have been studied before, demonstrating a mix of tolerability and side effects.

The C5VD chemotherapy regimen includes cisplatin, doxorubicin hydrochloride, fluorouracil, and vincristine sulfate. Studies have shown it is a standard treatment for certain cancers. It has been used effectively, but like many chemotherapy treatments, it can cause side effects. Patients have experienced nausea, hair loss, and low blood counts, which are common with these drugs.

The VIT chemotherapy regimen involves vincristine sulfate, irinotecan hydrochloride, and temsirolimus. It has been tested in children with high-risk liver cancer. Research suggests it can be effective but may lead to similar side effects, including tiredness, diarrhea, and low blood counts.

Overall, these treatments have been extensively studied for safety and effectiveness. They have shown potential benefits in treating liver cancer, though side effects are part of the treatment experience. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatment plans because they tailor therapy based on the risk level of liver cancer in patients, potentially improving outcomes and reducing unnecessary treatment. Unlike standard treatments that might use a one-size-fits-all approach, this method uses a combination of surgery and a mix of chemotherapy drugs such as cisplatin, fluorouracil, and vincristine sulfate, depending on the patient's risk group. This risk-based strategy aims to maximize effectiveness while minimizing side effects, offering a more personalized treatment experience. Moreover, the introduction of drugs like irinotecan hydrochloride and temsirolimus in high-risk patients could provide new avenues for tackling aggressive liver cancer forms. Researchers hope these tailored approaches will lead to better survival rates and quality of life for patients.

What evidence suggests that this trial's treatments could be effective for liver cancer?

This trial tests different treatment regimens for liver cancer based on risk levels. Participants in the intermediate-risk group will receive a combination of cisplatin, fluorouracil, vincristine, and doxorubicin (C5VD), which previous studies have found effective for treating hepatoblastoma, a type of liver cancer. These drugs work together to stop cancer cell growth and can improve survival rates. For the high-risk group, participants will receive vincristine and irinotecan (VI), which research has shown can shrink tumors and make surgery more successful. Additionally, the trial tests the combination of vincristine, irinotecan, and temsirolimus (VIT) for its potential to improve outcomes in children with aggressive liver cancer. These treatments aim to target cancer cells more effectively, offering hope for better control and outcomes in liver cancer treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Howard M Katzenstein

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/14689231/

The efficacy of the combination therapy of 5-fluorouracil, ... Purpose: Several clinical trials in human neoplasms have demonstrated the effectiveness of combination therapy with 5-fluorouracil (FUra), cisplatin (CDDP), and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03533582

Study Details | NCT03533582 | Cisplatin and Combination ... This partially randomized phase II/III trial studies how well, in combination with surgery, cisplatin and combination chemotherapy works in treating ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20458953

Clinical Trials The purpose of this study is to determine how well cisplatin and combination chemotherapy works in treating children and young adults with hepatoblastoma or ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11772854/

Exploring the efficacy of fluorouracil and platinum based ... Our study showed that 5-FU plus platinum-based chemotherapy can provide a limited but notable extension in survival duration for selected ...

5. withpower.com withpower.com/trial/phase-2-and-3-liver-neoplasms-4-2018-b0194

Combination Chemotherapy for Liver Cancer Cisplatin-based chemotherapy significantly improves survival and symptom control in stage IV non-small cell lung cancer patients with good performance status, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9066555/

Doxorubicin in Combination with Cisplatin/5-Flourouracil ... Cisplatin/5-flourouracil/vincristine (C5V) has been the standard regimen used in the North American cooperative group/Children's Oncology Group (COG) protocols ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03533582

Study Details | NCT03533582 | Cisplatin and Combination ... GROUP E2 (PLADO): Patients with de novo HCC receive cisplatin IV over 6 hours on day 1 and doxorubicin IV over 1-15 minutes on days 1 and 2 following surgery.

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34014

Doxorubicin in combination with cisplatin, 5‐flourouracil, and ... Patients were to receive 6 cycles of cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD): cisplatin (100 mg/m2 per dose or 3.3 mg/kg ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34762296/

Doxorubicin in combination with cisplatin, 5-flourouracil, and ... Doxorubicin in combination with cisplatin, 5-flourouracil, and vincristine is feasible and effective in unresectable hepatoblastoma: A ...

10. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT00980460/

Clinical Trial: NCT00980460 This phase III trial studies the side effects and how well risk-based therapy works in treating younger patients with newly diagnosed liver ...