Combination Chemotherapy for Liver Cancer

Not currently recruiting at 226 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Investigational drugs, Anticancer agents, St. John's wort

Disqualifiers: Prior chemotherapy, Uncontrolled infection, Organ transplant, 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: 1

Duration: 6-8 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether different combinations of chemotherapy drugs, along with surgery, can effectively treat liver cancer in children and young adults. The focus is on two types of liver cancer: hepatoblastoma and hepatocellular carcinoma. By using a mix of drugs like cisplatin and doxorubicin, the trial seeks to find the most effective way to stop cancer cells from growing and spreading. Those newly diagnosed with either of these liver cancers and who have not yet received chemotherapy or other treatments might be suitable for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other anticancer agents or certain drugs like St. John's wort if you are in Group D. It's best to discuss your current medications with the trial team.

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

Studies have shown that the treatments in this trial, including drugs like cisplatin and doxorubicin, have been used safely in various situations. Research indicates that cisplatin is generally well-tolerated for liver cancer, though some patients may experience side effects like nausea and kidney problems. Doxorubicin, another chemotherapy drug, can cause side effects such as hair loss and low blood cell counts, but these are usually manageable with supportive care.

Fluorouracil is also part of some treatment plans and is considered safe for patients with liver issues, although it can cause mouth sores and diarrhea. Vincristine sulfate is effective but may lead to nerve damage, causing tingling or numbness in the hands and feet.

Etoposide is often well-tolerated but can lower white blood cell counts, increasing the risk of infection. Irinotecan can cause significant side effects, including diarrhea and low blood cell counts, but these are usually controllable with medication.

Sorafenib, used in some combinations, is known to improve survival in liver cancer patients but might cause side effects like fatigue and high blood pressure. Gemcitabine, often paired with cisplatin, can cause liver enzyme elevations but is manageable.

Oxaliplatin and carboplatin are other chemotherapy drugs used in this trial. Oxaliplatin is generally considered safe, though it may cause nerve damage. Carboplatin is rarely linked to liver injury but can cause low blood counts.

These drugs have undergone extensive testing in many studies and are commonly used in chemotherapy combinations. While side effects are possible, they are typically well-known and can be managed with care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver cancer because they combine multiple chemotherapy drugs in different regimens to target the cancer more effectively. Unlike standard treatments that often rely on single or fewer agents, these combinations employ drugs like cisplatin, doxorubicin, and sorafenib, among others, to attack the cancer cells from multiple angles. Some regimens include surgical options after specific cycles, which can help in reducing tumor size and improving outcomes. This multipronged approach could potentially lead to better control of the disease and improve survival rates. The study also explores novel sequences and combinations, which might offer insights into more effective liver cancer treatments in the future.

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

Research shows that cisplatin, when combined with other chemotherapy drugs, can effectively treat liver cancer. In this trial, participants may receive different combinations of cisplatin with other drugs. One arm of the trial combines cisplatin with doxorubicin, which studies have shown to yield a 5-year survival rate of up to 75%. Another arm involves cisplatin with gemcitabine and oxaliplatin, which demonstrated about a 25% response rate, with many patients experiencing stable disease. Additionally, some participants will receive combinations with sorafenib, a targeted therapy, which research has found to be more effective than using a single drug. These combinations often stop tumor growth and improve survival chances, offering hope for those with liver cancers such as hepatoblastoma or hepatocellular carcinoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Gregory M Tiao

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and young adults with hepatoblastoma or liver cancer who have undergone surgery. They must be newly diagnosed, have proper organ function, not received prior cancer treatments except certain surgeries, and agree to contraception if of childbearing potential. Those with uncontrolled infections or on other cancer drugs can't join.

Inclusion Criteria

I am too ill for a biopsy but meet all other trial requirements.

My kidney function is normal or near normal.

For all Group A patients, WDF status as determined by rapid review will be used to further stratify patients to Group A1 or A2

Exclusion Criteria

I have had a liver transplant for liver cancer but no other organ transplants.

Patients who are currently receiving other anticancer agents

Patients with hypersensitivity to any drugs on their expected treatment arm

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cisplatin and combination chemotherapy, with treatment cycles varying by risk group and tumor resectability

6-8 months

Multiple visits for chemotherapy administration

Surgery

Surgical resection of tumors, performed after initial chemotherapy cycles

1-2 weeks

1 visit for surgery

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes after treatment

Up to 5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Doxorubicin, Fluorouracil, Vincristine Sulfate, Etoposide, Irinotecan, Sorafenib, Gemcitabine, Oxaliplatin, Carboplatin
• Resection

Trial Overview

The study tests how well cisplatin combined with other chemotherapy drugs works after surgery in treating liver cancers in the young. It's a phase II/III trial where these drugs are given to see if they're better at killing tumor cells than one drug alone.

How Is the Trial Designed?

Group I: GROUP F ARM 2 (P/GEMOX) Experimental Treatment 7 Interventions

Patients receive cisplatin IV over 6 hours on day 1, doxorubicin IV over 1-15 minutes on days 1 and 2 and sorafenib PO BID on days 3-14 of cycles 1 and 3. Patients also receive gemcitabine IV over 90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 and sorafenib PO on days 1-14 of cycles 2 and 4. Patients may undergo surgery, if tumors are resectable, or receive an additional 4 cycles of the treatment. Patients may optionally undergo blood sample collection on study.

Group II: GROUP F ARM 1 (PLADO) Experimental Treatment 4 Interventions

Patients receive cisplatin IV over 6 hours on day 1, doxorubicin IV over 1-15 minutes on days 1 and 2 and sorafenib PO BID on days 3-21. Treatments repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo surgery, if tumors are resectable, or receive an additional 3 cycles of the treatment. Patients may optionally undergo blood sample collection on study.

Group III: GROUP E2 (PLADO) Experimental Treatment 3 Interventions

Patients receive cisplatin IV over 6 hours on day 1 and doxorubicin IV over 1-15 minutes on days 1 and 2 following surgery. Treatments repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo blood sample collection on study.

Group IV: GROUP D2 ARM VI Experimental Treatment 6 Interventions

SIOPEL-4 IV INDUCTION: Patients receive cisplatin IV over 6 hours on days 1, 8, and 15 (for cycles 1 and 2) and days 1 and 8 (for cycle 3) and doxorubicin IV over 1-15 minutes on days 8 and 9. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients receive carboplatin IV over 1 hour on days 1 and 2 and doxorubicin IV over 1-15 minutes on days 1 and 2 during cycles 1, 3 and 5. Patients also receive vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan IV over 90 minutes QD on days 1 to 5 of cycles 2, 4 and 6. Treatments repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo blood sample collection on study.

Group V: GROUP D2 ARM CE Experimental Treatment 5 Interventions

SIOPEL-4 IV INDUCTION: Patients receive cisplatin IV over 6 hours on days 1, 8, and 15 (for cycles 1 and 2) and days 1 and 8 (for cycle 3) and doxorubicin IV over 1-15 minutes on days 8 and 9. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients receive carboplatin IV over 1 hour on days 1 and 2, doxorubicin IV over 1-15 minutes on days 1 and 2 during cycles 1, 3 and 5, and carboplatin over 1 hour and etoposide IV over 2 hours on day 1 and 2 of cycles 2, 4 and 6. Treatments repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo blood sample collection on study.

Group VI: GROUP D1 Experimental Treatment 4 Interventions

SIOPEL-4 INDUCTION: Patients receive cisplatin IV over 6 hours on days 1, 8, and 15 (for cycles 1 and 2) and days 1 and 8 (for cycle 3) and doxorubicin IV over 1-15 minutes on days 8 and 9 during cycles 1 and 2 and days 1 and 2 during cycle 3. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients with lung complete remission (either with chemotherapy and/or surgery) receive carboplatin IV over 1 hour on day 1 and doxorubicin IV over 1-15 minutes on days 1 and 2. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo blood sample collection on study.

Group VII: GROUP C ARM CDDP Experimental Treatment 3 Interventions

Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after cycle 2 or 4. Patients may optionally undergo blood sample collection on study.

Group VIII: GROUP C ARM C5VD Experimental Treatment 5 Interventions

Patients receive cisplatin IV over 6 hours on day 1, 5-fluorouracil IV over 1-15 minutes, vincristine sulfate IV over 1 minute on days 1, 8, and 15 and doxorubicin IV over 1-15 minutes on days 1 and 2. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after cycle 2 or 4. Patients may optionally undergo blood sample collection on study.

Group IX: GROUP B2 ARM II Experimental Treatment 2 Interventions

Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 6 total cycles. Patients may optionally undergo blood sample collection on study.

Group X: GROUP B2 ARM I Experimental Treatment 3 Interventions

Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 6 total cycles (4 pre-surgery, 2 post-surgery). After cycle 4, patients undergo surgery, then continue with 2 additional cycles of cisplatin. Patients may optionally undergo blood sample collection on study.

Group XI: GROUP B1 ARM 6-CDDP Experimental Treatment 3 Interventions

Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for 6 cycles (2 pre-surgery, 4 post-surgery) in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo blood sample collection on study.

Group XII: GROUP B1 ARM 4-CDDP Experimental Treatment 2 Interventions

Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for 4 cycles (2 pre-surgery, 2 post-surgery) in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo blood sample collection on study.

Group XIII: GROUP A2 (NON-WDF) Experimental Treatment 2 Interventions

Patients receive cisplatin IV over 6 hours on day 1 following surgery. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo blood sample collection on study.

Group XIV: Group A1 (WDF) Active Control 2 Interventions

Patients undergo observation. Patients may optionally undergo blood sample collection on study.

Group XV: GROUP E1 Active Control 3 Interventions

Patients undergo observation only. Patients may optionally undergo blood sample collection on study.

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?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II trial involving 37 patients with advanced non-small cell lung cancer, the combination of carboplatin and gemcitabine showed promising efficacy, with 8.1% achieving complete response and 24.3% achieving partial response after treatment.

The treatment was well-tolerated, with mild hematological toxicity, and a median survival of 10 months, suggesting that this regimen could be a viable palliative option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and gemcitabine in the palliative treatment of stage IV non-small cell lung cancer: definitive results of a phase II trial. Tassinari, D., Fochessati, F., Arcangeli, V., et al.[2022]

Cisplatin combined with either a vinca alkaloid or etoposide is highly effective in reducing mortality for patients with non-small cell lung cancer, as shown in meta-analyses comparing chemotherapy to supportive care.

Recent studies indicate that combining cisplatin-based chemotherapy with new agents and radiotherapy can significantly prolong survival and improve outcomes for patients with locally advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for non-small cell lung cancer]. Shinkai, T., Saijo, N.[2018]

In a randomized phase II trial involving 78 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of pemetrexed with carboplatin showed a median survival time of 10.4 months and a response rate of 39.5%, indicating it is an effective treatment option.

Both pemetrexed/cisplatin and pemetrexed/carboplatin combinations were well-tolerated, with manageable hematologic toxicities, suggesting that these treatments can be safely administered as first-line therapy for ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of pemetrexed combined with either cisplatin or carboplatin in untreated extensive-stage small-cell lung cancer. Socinski, MA., Weissman, C., Hart, LL., et al.[2015]

Cisplatin and carboplatin are both effective platinum-based chemotherapy agents, but they differ significantly in their side effects; cisplatin can cause severe kidney damage and neurotoxicity, while carboplatin is safer for renal function and has less neurotoxicity.

Carboplatin's toxicity profile allows for dose adjustments based on renal function, making it a more manageable option for patients, whereas cisplatin requires hydration protocols to mitigate its harmful effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative adverse effect profiles of platinum drugs. McKeage, MJ.[2018]

Cisplatin-based chemotherapy significantly improves survival and symptom control in stage IV non-small cell lung cancer patients with good performance status, suggesting its effectiveness as a primary treatment option.

Combination regimens including cisplatin and at least one other active drug (like ifosfamide or gemcitabine) are recommended, with four to six cycles proposed for patients who respond well, while non-platinum options can be considered for those unable to tolerate platinum-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stage IV NSCLC. Place of chemotherapy]. Meert, AP.[2013]

Less than 25% of patients with non-small cell lung cancer (NSCLC) have early-stage disease that can be surgically removed, highlighting the need for effective treatments for advanced stages.

Cisplatin-based chemotherapy, especially in combination with newer agents like gemcitabine and paclitaxel, has shown improved survival rates and response rates exceeding 35% in advanced NSCLC, indicating its efficacy in managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on European randomized studies in non-small cell lung cancer. Giaccone, G., Manegold, C., Rosell, R., et al.[2007]

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