Solid Tumors
Conditions
Brief summary
The purpose of this study is to evaluate the effect of trametinib once daily on the pharmacokinetics (PK) of a daily dosing oral contraceptives (OCs) containing norethindrone (NE) and ethinyl estradiol (EE) in female patients with solid tumors. The PK of trametinib and its metabolite M5 will also be assessed.
Interventions
DRUGTrametinib
Each tablet is 2mg trametinib to be taken orally once daily.
DRUGOral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol)
Combined oral contraceptive to be taken orally once daily.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 59 Years
Healthy volunteers
No
Inclusion criteria
* Has a histologically or cytologically confirmed diagnosis of a solid tumor malignancy (except for any excluded malignancies listed in the
Exclusion criteria
) that is not responsive to standard therapy(ies) or for which there is no approved therapy. * Meets one of the following criteria: Is currently on a stable regimen of an oral contraceptive containing 1mg NE and 0.035mg EE, or Is willing to switch to a regimen of an oral contraceptive containing 1mg NE and 0.035mg EE from a stable regimen of an alternate OC, or Is willing to start a regimen of an oral contraceptive containing 1mg NE and 0.035mg EE. * Meets one of the following criteria: Is post-menopausal, or, Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during dosing and for four months after stopping medication. * Has no prior treatment-related toxicities \>Grade 1 (except alopecia) at the time of enrolment. * Patient must meet the following laboratory values at the screening visit: Absolute Neutrophil Count ≥1.5 x 109/L. Platelets ≥75 x 109/L. Hemoglobin (Hgb) ≥9 g/dL. Serum creatinine \<1.5 mg/dL. Total bilirubin ≤1.5 x upper limit of normal (ULN) (isolated bilirubin \>1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). Aspartate transaminase (AST) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST ≤5.0 x ULN. Alanine transaminase (ALT) ≤ 3.0 x ULN, except for patients with liver metastasis or tumor infiltration, who may only be included if ALT ≤5.0 x ULN. Prothrombin time (PT)/International normalized ratio (INR) and Partial thromboplastin time (PTT) ≤1.5xULN. Note: patients receiving therapeutic anticoagulation agents prior screening are permitted. Albumin 2.5 g/dL. * Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics parameter: Tmax of NE and EE alone and incombination with trametinib | Days 5 and 6 and 21 and 22 | To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors. |
| Pharmacokinetics parameter: AUCtau of NE and EE alone and in combination with trametinib | Day 5 and 6 and 21 and 22 | To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors. |
| Pharmacokinetics parameter: AUClast of NE and EE alone and in combination with trametinib | Day 5 and 6 and 21 and 22 | To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors. |
| Pharmacokinetics parameter: Cmax of NE and EE alone and in combination with trametinib | Day 5 and 6 and 21 and 22 | To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics parameter: AUClast of M5 | Day 21 and 22 | Characterize PK of metabolite M5 |
| Pharmacokinetics parameter: AUCtau of M5 | Day 21 and 22 | Characterize PK of metabolite M5 |
| Pharmacokinetics parameter: Cmax of M5 | Day 21 and 22 | Characterize PK of metabolite M5 |
| Pharmacokinetics parameter: Tmax of M5 | Day 21 and 22 | Characterize PK of metabolite M5 |
Countries
Belgium, Netherlands, Spain, United Kingdom, United States
Outcome results
None listed