Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize Effects of a Moderate CYP3A Inhi… (NCT03028103) | Clinical Trial Compass
CompletedPhase 1
Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize Effects of a Moderate CYP3A Inhibitor on PK of Tazemetostat, Effects of Tazemetostat on PK of CYP2C8 and CYP2C19 Substrates, and Effect of Increased Gastric pH on PK of Tazemetostat in B-cell Lymphoma or Advanced Solid Tumor Patients
United States32 participantsStarted 2017-03-27
Plain-language summary
This is a Phase 1, open-label, two-part, safety, PK, and activity study designed to characterize the DDI potential of tazemetostat. Tazemetostat will be taken orally BID continuously in 28-day cycles in both study parts.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Male or female ≥ 18 years of age at time of consent
✓. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
✓. Has the ability to understand informed consent and provided signed written informed consent
✓. Has histologically confirmed diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL) and have relapsed or refractory disease following at least two lines of prior standard therapy, including alkylator/anthracycline (unless anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (R-CHOP; rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone or prednisone, or equivalent) AND must be considered unable to benefit from intensification treatment with autologous hematopoietic stem cell transplantation (ASCT), as defined by meeting at least one of the following criteria:
✓. Relapsed following, or refractory to, previous ASCT
✓. Did not achieve at least a partial response (PR) to a standard salvage regimen (e.g., R-ICE; rituximab, ifosfamide, carboplatin, etoposide, or R-DHAP; rituximab, dexamethasone, cytarabine, cisplatin)
✓. Ineligible for intensification treatment due to age or significant comorbidity
✓. Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
Exclusion criteria
✕. Is pregnant or nursing
What they're measuring
1
Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8)
Timeframe: Days 15 and 19, 0 to 8 hours post-dose
2
Part A: Cmax of Tazemetostat During Co-administration With Fluconazole
Timeframe: Days 15 and 19, 0 to 8 hours post-dose
3
Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞)
Timeframe: Days 1 and 16, 0 to 8 hours post-dose
4
Part B: Cmax of Repaglinide During Co-administration With Tazemetostat
Timeframe: Days 1 and 16, 0 to 8 hours post-dose
5
Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞)
Timeframe: Days 1 and 16, 0 to 8 hours post-dose
6
Part B: Cmax of Omeprazole During Co-administration With Tazemetostat
Timeframe: Days 1 and 16, 0 to 8 hours post-dose
7
Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8)
. Has active central nervous system (CNS) or leptomeningeal metastasis
✕. Has had a prior malignancy other than the malignancies under study Exception: Subject who has been disease-free for 3 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
✕. Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) and any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
✕. Has a prior history of T-LBL/T-ALL.
✕. Has had major surgery within 3 weeks prior to enrollment NOTE: Minor surgery (e.g., minor biopsy, central venous catheter placement) is permitted within 3 weeks prior to enrollment.
✕. Is unwilling to exclude grapefruit juice, Seville oranges, and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
✕. Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
8
Part B: Cmax of Tazemetostat During Co-administration With Omeprazole