A Study on the Effect of Tazametostat (study drug) in Patients with Advanced Solid Tumors or with B Cell Lymphomas
- Conditions
- Relapsed or refractory Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Advanced solid tumorMedDRA version: 20.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10003899 Term: B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-004083-21-DE
- Lead Sponsor
- Epizyme, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 350
All Subjects:
1. Phase 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Phase 2: ECOG performance status of 0 to 2.
2. Life expectancy = 3 months before starting tazemetostat.
3. Subjects with a history of Hepatitis B or C are eligible on the condition that subjects have adequate liver function as defined by Inclusion Criterion #6 and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV RNA).
4. Adequate renal function defined as calculated creatinine clearance = 40 mL/min per the Cockcroft and Gault formula or local institutional standard formula.
5. Adequate bone marrow function:
a. Absolute neutrophil count (ANC)= 750/mm3 (= 0.75 × 109/L)
b. Platelets = 75,000/mm3 (= 75 × 10*9/L)
c. Hemoglobin = 9.0 g/dL
6. Adequate liver function:
a. Total bilirubin = 1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert’s syndrome
b. Alkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) = 3 × ULN (= 5 × ULN if subject has liver metastases)
7. Time between prior anticancer therapy and first dose of tazemetostat as indicated in the protocol.
8. Males or females aged =18 years at the time of informed consent (Phase 2). Males and females aged =16 years of age at time of informed consent (Phase 1).
9. Females must not be lactating or pregnant at screening or baseline (as documented by a negative beta-human chorionic gonadotropin [ß-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutively amenorrheic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception(as per protocol), from the last menstrual period prior to randomization, during Treatment Cycles, and for 30 days after the final dose of study drug, and have a male partner who uses a condom.
10. Male subjects must have had either a successful vasectomy OR they and their female partner must meet the criteria above (ie, not of childbearing potential OR practicing highly effective contraception and use a condom throughout the study period and for 30 days after study drug discontinuation).
11. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
Phase 1 only (IGR and IB sites in France only):
12. Histologically and/or cytologically confirmed advanced or metastatic solid tumor or B cell lymphomas that have progressed after treatment with approved therapies or for which there are n
All Subjects:
1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
2. Subjects with known leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
3. Has thrombocytopenia, neutropenia, or anemia of Grade =3 (per CTCAE 4.03 criteria) and any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
4. Has a prior history of T-LBL/T-ALL.
5. Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St John's Wort)
6. Subjects unwilling to exclude Seville oranges, grapefruit juice, and grapefruit from their diet.
7. Any prior treatment-related (ie, chemotherapy, immunotherapy, radiotherapy), clinically significant toxicities have not resolved to = Grade 1 per CTCAE version 4.03, or prior treatment-related toxicities are clinically unstable and clinically significant at time of enrollment.
8. Major surgery within 4 weeks before the first dose of study drug.
9. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of tazemetostat.
10. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia.
11. Prolongation of corrected QT interval using Fridericia’s formula (QTcF) to > 480 msec.
12. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.
13. Active infection requiring systemic therapy.
14. Known hypersensitivity to any component of tazemetostat, prednisolone/prednisone (combination cohort only), or inability to be treated with a Pneumocystis prophylaxis medication (combination cohort only).
15. Immunocompromised subjects, including subjects known to be infected with human immunodeficiency virus (HIV).
16. Any other major illness that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in this study.
17. Females who are pregnant or breastfeeding.
18. Subjects who have undergone a solid organ transplant.
Phase 2 only:
19. Subjects with noncutaneous malignancies other than B cell lymphomas.
? Exception: Subjects with another malignancy who have been disease-free for 5 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method