Introduction

This family protocol summary provides a general overview of the Children’s Oncology Group (COG) study ARST1321. It tells who is eligible and gives basic information about the study. More details about the study are in the consent form. You can get this from your oncologist.

ARST1321 is a Phase 2/3 clinical trial. A trial is another word for a study. This study (clinical trial) is a therapeutic clinical trial. The purpose of a Phase 2 trial is to learn if a new treatment works in treating a type of cancer and how it affects the body. In a Phase 2 trial, patients with a specific type of cancer receive a new treatment using a dose that was found to be safe in a Phase I trial. Patients are checked for side effects of the treatment and to see whether the cancer shrinks or goes away.

The purpose of a Phase 3 trial is to learn if a new treatment that is known to work in treating a type of cancer is better in some way than the standard treatment. That means it is done to learn more about how well treatments work and the side effects of the treatments. For example, does it have better cure rates, longer control of disease, fewer or less serious side effects, or fewer days in the hospital?

ARST1321 compares 2 treatments. These treatments are called study arms. Usually, one study arm is the standard or the best proven current treatment. The other study arms have some changes or additions. The new treatment is thought to be at least as good as the standard treatment. It is not known if the new treatment will be better than the standard treatment.

In a Phase 3 trial, each child is assigned to a study arm by a method called randomization. This is a process like flipping a coin that assures that each child has a fair and equal chance of being assigned to any of the study arms. This way the study arms can be compared fairly.

In most clinical trials, we will not know which treatment is better until all of the children taking part in the trial have completed treatment and have been followed for several years. If one of the treatments is found to be better or safer than the others while the trial is still on-going, the trial will be stopped. All children still in the trial will be given the treatment with the best results when possible.

It is important to understand that participating in a clinical trial is voluntary. The decision about whether or not to participate will not affect the care provided by the health care team in any way. You can find additional information about participation in clinical trials at www.childrensoncologygroup.org Always discuss any questions that you may have with your health care team.

Study Number

ARST1321

Official Title

Pazopanib Neoadjuvant Trial in Non-Rhabdomyosarcoma Soft Tissue Sarcomas: A Phase 2/3 Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib

Study Opening Date

The Phase II portion of ARST1321 opened in July 2014. The study was temporarily closed on October 18, 2018 as the ARST1321 committee reviews the results to determine if the trial will open as a Phase 3 trial. The ARST1321 committee hopes to enroll an additional 140 patients on the phase III portion of the trial. It is expected that this study will remain open for 4 - 5 years and enroll a total of 340 patients.

General Patient Eligibility

• Age: 2 years of age or older
• Patients must be able to swallow whole tablets
• Diagnosis: Newly diagnosed, unresectable (unable to be surgically removed), intermediate-risk and high-risksoft tissue sarcomas other than rhabdomyosarcoma (n on-rhabdomyosarcoma soft tissue sarcoma, or NRSTS) located in the extremity or trunk

Please consult your doctor to determine whether your child may participate in this study.

General Background and Study Goal

The treatment for children and adults with intermediate-risk and high-risk NRSTS includes surgery and radiation, with or without chemotherapy. In spite of treatment, the response rate and survival for patients remains low. New therapies are needed to improve the outcome for people with NRSTS.

Researchers want to know if survival for NRSTS can be improved by adding a new drug, called pazopanib. Pazopanib targets a class of enzymes called tyrosine kinases that are important in cell growth and cell survival. Pazopanib has been shown to be effective in adults with a variety of sarcomas. Survival was improved in patients with certain types of sarcomas treated with pazopanib. Pazopanib has also been studied in small groups of children in Phase 1 trials with some tumor responses noted. There is also information that giving pazopanib with chemotherapy and/or radiation will add to the effect of both pazopanib and standard chemotherapy and radiation.

This study will be done in two phases. The phase 2 portion of the study will determine whether patients who receive pazopanib respond better to treatment.

In the phase 3 portion of ARST1321, doctors hope to learn if the addition of pazopanib to the standard treatment of chemotherapy and radiation will improve overall survival of patients with NRSTS without adding unacceptable side effects

Summary of the Treatment

All patients will receive standard chemotherapy, surgery and radiation therapy. The non-chemotherapy arms of the study have been closed.

The phase 2 portion of the study is divided into two parts.

• November 21, 2016: Part 1 of the phase 2 portion of the study was completed, and the dose level of pazopanib has been determined.
• October 18, 2018: One of the primary endpoints of the phase 2 portion of the study, the achievement of greater than 90% tumor death on the Pazopanib arm at the time of surgery, was reached. The study has been temporarily closed to accrual.

All patients will receive chemotherapy and radiation therapy. They will be randomized between two treatment plans:

• Regimen A (Standard Chemotherapy & Radiation plus Pazopanib)
• Regimen B (Standard Chemotherapy & Radiation)

Treatment will consist of several phases:

• Induction
  • 13 weeks for the chemotherapy group
• Surgical resection of the primary tumor
• Continuation
  • up to 10 weeks for the chemotherapy group

Patients on regimen A will receive Pazopanib daily during Induction and Continuation.

If phase 2 shows that patients who receive pazopanib respond better to treatment, the phase 3 portion of the study will open.

Special Considerations

• Pazopanib must be swallowed whole and cannot be crushed or broken, so patients must be able to swallow tablets in order to be eligible for this study.
• Patients younger than 18 years of age receiving pazopanib will have x-rays of the knees before treatment begins and possibly again at the end of treatment due to concerns of growth disturbances in young people who take pazopanib.

Risks and Side Effects

Chemotherapy can cause side effects during and after treatment. All patients will be closely monitored for possible side effects of the medicines. All risks and side effects will be explained by your treatment team during the consent process. They can answer any questions that you may have about giving permission for your child to be in the clinical trial or other aspects of care. Please refer to the consent form for a detailed explanation of the side effects associated with the treatment on this study.

Contact Information

Your child’s oncologist and nurses are the best sources for further information.

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS