A Study on the Effect of Tazemetostat (study drug) in Patients with Advanced Solid Tumors or with B Cell Lymphomas
- Conditions
- Relapsed or refractory Diffuse Large B Cell Lymphoma, FollicularLymphoma, Advanced solid tumorTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-004083-21-GB
- Lead Sponsor
- Epizyme, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 420
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 [ßhCG]
test with a minimum sensitivity of 25 IU/L or equivalent units of ßhCG).
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 no standard therapies
available.
Phase 2:
13. Subjects must satisfy all of the following criteria:
a. Have histologically confirmed DLBCL (including primary mediastinal B
cell lymphoma), with relapsed or refractory disease following at least 2
lines of prior standard ther
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 (cohort 6 only), or inability to be
treated with a Pneumocystis prophylaxis medication (cohort 6 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 diseasefree
for 5 years, or subjects with a history of a completely resected nonmelanoma
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