Gastroenterology

This partially randomized phase II/III trial studies how well, in combination with surgery, cisplatin and combination chemotherapy works in treating children and young adults with hepatoblastoma or hepatocellular carcinoma. Drugs used in chemotherapy, such as cisplatin, doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan, sorafenib, gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving combination chemotherapy may kill more tumor cells than one type of chemotherapy alone.

The investigators will enroll a total of 628 patients under 18 years of age with ARP or CP. Included in the total are the 357patients in the INSPPIRE 1 database who are planned to be reenrolled under this protocol over the next 4 years. Patient questionnaires and physician surveys will be applied at the time of enrollment and annually thereafter as long as possible. At the first study visit after turning 18 years of age, the patient will sign the informed consent to continue in the study. Specifically, the investigators will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.

In this study, researchers are learning more about RTA 408, also known as omaveloxolone, BIIB141, or SKYCLARYS®. The main goal of this study is to learn more about the safety of RTA 408 and how it affects physical effort, movement, coordination, and how participants feel in daily life.

The main questions researchers want to answer in this study are:

* How much physical effort can a participant produce during a cycling test after 12 weeks of treatment?
* How do scores on the modified Friedreich's Ataxia Rating Scale (mFARS) change after 48 weeks?

Researchers will use the modified Friedreich's Ataxia Rating Scale (mFARS) to measure how FA affects the nervous system. The mFARS looks at movement ability, balance, coordination, speech, and how well the arms and legs work.

They will also use a cycling test to measure physical effort, along with questionnaires to learn how participants feel and function in daily life.

Safety will also be tested using physical exams, vital sign checks, echocardiograms (ECHO), electrocardiograms (ECG), and blood and urine tests.

The study will be done in 2 main parts, followed by an optional Extension period:

* In Part 1, participants will be randomly assigned to take different doses of RTA 408 or a placebo by mouth once a day for 12 weeks. A placebo looks like the study drug but contains no real medicine.
* Researchers will compare these doses to decide which one to use in Part 2.
* In Part 2, a different group of participants will take either the chosen dose of RTA 408 (150 mg) or placebo once a day for 48 weeks.
* Participants who complete Part 1 or Part 2 may be able to join an Extension period, where everyone receives RTA 408.
* In the Extension period, participants will continue to receive RTA 408 until the drug becomes commercially available or until they leave the study
* Participants in Part 1 will have up to 9 study visits and 2 phone calls. If they do not move onto the Extension period, they will stay in the study for up to 20 weeks.
* Participants in Part 2 will have up to 10 study visits and 3 phone calls. If they do not move onto the Extension period, they will stay in the study for up to 61 weeks.
* Participants in the Extension period will have 2 visits in the first month, followed by visits every 6 months.