Tazemetostat in Combination With Doxorubicin as Frontline Therapy for Advanced Epithelioid Sarcoma

Launched by EPIZYME, INC. · Dec 17, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with advanced epithelioid sarcoma, a rare type of cancer that affects soft tissues in the body. The trial is testing a drug called tazemetostat in combination with doxorubicin, which is a standard treatment for this type of cancer. The main goal is to see if this combination can help patients live longer without their disease getting worse. The trial is divided into two parts: the first part will check how safe the treatment is and find the best dose, while the second part will compare how well the combination works against a placebo (a dummy treatment) along with doxorubicin.

To participate in this trial, patients need to be at least 18 years old and have a confirmed diagnosis of advanced epithelioid sarcoma. They also need to be in generally good health and able to tolerate the study treatments. Participants will need to provide written consent and will undergo regular check-ups during the trial. Importantly, women who are pregnant or breastfeeding cannot participate, and there are specific health criteria that must be met to ensure safety. If you or a loved one are considering joining this trial, it’s a chance to potentially access a new treatment that could make a difference in managing this challenging cancer.

Gender

ALL

Eligibility criteria

• • Inclusion Criteria
• Participants must meet ALL the following inclusion criteria to be eligible to enroll in this study:
• • 1. Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol. Study related activities will not start until written consent is obtained.
• • 2. Life expectancy ≥ 3 months before enrollment
• • 3. Phase 1b: 18-65 years old histologically confirmed Soft Tissue Sarcoma
• • 4. Phase 3: ≥18 years old with unresectable locally advanced or metastatic Epithelioid Sarcoma and tumor tissue available
• • 5. Have measurable disease
• • 6. ECOG performance status of 0, 1, or 2
• • 7. Have adequate hematologic (bone marrow \[BM\] and coagulation factors), renal and hepatic function as required per protocol
• • 8. Females must not be lactating or pregnant at Screening or Baseline
• • 9. Females must not be pregnant or breast feeding and agree to use highly effective contraception during the clinical trial and for 6 months following the final dose of study
• • 10. Male participants of child-bearing potential must have had either a successful vasectomy or practice highly effective contraception
• • 11. Participants diagnosed with human immunodeficiency virus (HIV) are eligible to participate in the study if their infection is well controlled on anti-retroviral therapy.
• • Exclusion Criteria
• Participants meeting ANY of the following exclusion criteria are NOT eligible to enroll in this study:
• • 1. Prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2).
• • 2. Prior systemic anticancer therapy.
• • 3. Contraindications noted in the doxorubicin label
• • 4. Have any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• • 5. Have prior history of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia (T- LBL/T-ALL).
• • 6. Have participated in another interventional clinical study and received investigational drug within 30 days or 5 half-lives, whichever is longer, prior to the planned first dose of study treatment.
• • 7. Have known active central nervous system (CNS) or any leptomeningeal metastasis of primary extracranial tumor.
• • 8. Participants taking medications that are known potent cytochrome P450 (CYP)3A4 inducers/inhibitors (including St. John's Wort)
• • 9. Are unwilling to exclude Seville oranges, grapefruit juice, AND grapefruit from the diet and all foods that contain those fruits from time of enrollment to through the duration of study participation.
• • 10. Major surgery within 4 weeks before the first dose of study treatment. Participants must have recovered from surgery prior to enrollment to this study.
• • 11. Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of study treatment.
• • 12. Have an active infection requiring systemic therapy.
• • 13. Are immunocompromised (ie, has a congenital immunodeficiency).
• • 14. Have known hypersensitivity to any component of tazemetostat or doxorubicin.
• • 15. Cardiovascular impairment as stated in the protocol
• • 16. Have a known active infection with hepatitis B virus (HBV, as measured by positive hepatitis B surface antigen), hepatitis C virus (HCV, as measured by positive hepatitis C antibody).
• • 17. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the participant's participation in this study OR interfere with their ability to receive study treatment or complete the study.
• • 18. Female participants who are pregnant or breastfeeding.
• • 19. Participants who have undergone a solid organ transplant.
• • 20. Participants with malignancies other than STS (phase 1b) or ES (Phase 3 only).
• • 21. Participants housed in an institution by order of the authorities or courts.