Solid TumorsPhase 1NCT02705963
A Drug-Drug Interaction Study to Assess the Effect of Trametinib on the Pharmacokinetics of an Oral Contraceptive in Female Patients With Solid Tumors
A Phase 1 study testing Trametinib and Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol) in people with Solid Tumors, run by Novartis Pharmaceuticals at 7 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 59 years, women only
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Trametinib and Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 20 Oct 2016to 29 Aug 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease
- Has had any major surgery, extensive radiotherapy, or anti-cancer therapy (e.g., chemotherapy with delayed toxicity, biologic therapy, or immunotherapy) within 21 days prior to enrolment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrolment. Prolonged immobilization must have resolved prior to enrolment.
- Has a known or suspected carcinoma that is excluded as administration of Oral Contraceptive would be contraindicated.
- Has a history of another malignancy.
- Has a history of interstitial lung disease or pneumonitis.
- Has a history of RVO.
Show all 9Show fewer
- Has a history of any of conditions that would contraindicate administration of an OC
- Has symptomatic or untreated leptomeningeal, brain metastases, or spinal cord compression.
- Other protocol-defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
United States2 sites
Karmanos Cancer Institute Karmanos Cancer Institute
Detroit, Michigan, 48201
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Belgium2 sites
Novartis Investigative Site
Edegem, 2650
Novartis Investigative Site
Namur, 5000
About this study
Official title: A Phase I, Open-Label Study to Determine the Effect of Repeat Dosing of Trametinib on the Pharmacokinetics of a Combined Oral Contraceptive (Norethindrone Plus Ethinyl Estradiol) in Female Patients With Solid Tumors
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.
- Conditions
- Solid Tumors
- Being tested
- Trametinib, Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrametinibDrug
Each tablet is 2mg trametinib to be taken orally once daily.
TrametinibDrug
Each tablet is 0.5mg trametinib to be taken orally once daily. 0.5mg tablets may be used if a dose reduction is required.
Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol)Drug
Combined oral contraceptive to be taken orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Oral Contraceptive / Trametinib | Experimental | In treatment period 1 of the PK Phase patients will take the Oral Contraceptive once daily from Days 1-5. Period 2 of the PK Phase starts on Day 6 when patients take both the Oral Contraceptive and trametinib once daily from Days 6 to 21. Patients may continue dosing with trametinib only once daily from Day 22 onwards (post PK Phase). Receives: Drug: Trametinib; Drug: Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics parameter: AUCtau of NE and EE alone and in combination with trametinib
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.
Measured: Day 5 and 6 and 21 and 22
Pharmacokinetics parameter: AUClast of NE and EE alone and in combination with trametinib
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.
Measured: Day 5 and 6 and 21 and 22
Pharmacokinetics parameter: Cmax of NE and EE alone and in combination with trametinib
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.
Measured: Day 5 and 6 and 21 and 22
Pharmacokinetics parameter: Tmax of NE and EE alone and incombination with trametinib
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.
Measured: Days 5 and 6 and 21 and 22
Secondary outcomes (4)
Pharmacokinetics parameter: AUClast of M5
Characterize PK of metabolite M5
Measured: Day 21 and 22
Pharmacokinetics parameter: AUCtau of M5
Characterize PK of metabolite M5
Measured: Day 21 and 22
Pharmacokinetics parameter: Cmax of M5
Characterize PK of metabolite M5
Measured: Day 21 and 22
Pharmacokinetics parameter: Tmax of M5
Characterize PK of metabolite M5
Measured: Day 21 and 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2016 (estimated)
- Study start20 Oct 2016
- Primary completion29 Aug 2019
- Study completion29 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02705963
- Sponsor's protocol ID
- CTMT212X2102
- Status last verified
- Oct 2021
- First submitted
- 22 Feb 2016
- Last updated
- 9 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label Study to Determine the Effect of Repeat Dosing of Trametinib on the Pharmacokinetics of a Combined Oral Contraceptive (Norethindrone Plus Ethinyl Estradiol) in Female Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT02705963
- Acronym / sponsor ID
- CTMT212X2102
- Conditions
- Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Oct 2016 (actual)
- Primary completion
- 29 Aug 2019 (actual)
- Study completion
- 29 Aug 2019 (actual)
- First posted
- 11 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral Contraceptive / Trametinib | Experimental | Drug: Trametinib, Drug: Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol)In treatment period 1 of the PK Phase patients will take the Oral Contraceptive once daily from Days 1-5. Period 2 of the PK Phase starts on Day 6 when patients take both the Oral Contraceptive and trametinib once daily from Days 6 to 21. Patients may continue dosing with trametinib only once daily from Day 22 onwards (post PK Phase). |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease
- Has had any major surgery, extensive radiotherapy, or anti-cancer therapy (e.g., chemotherapy with delayed toxicity, biologic therapy, or immunotherapy) within 21 days prior to enrolment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrolment. Prolonged immobilization must have resolved prior to enrolment.
- Has a known or suspected carcinoma that is excluded as administration of Oral Contraceptive would be contraindicated.
- Has a history of another malignancy.
- Has a history of interstitial lung disease or pneumonitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrametinibEach tablet is 2mg trametinib to be taken orally once daily. | Drug | Oral Contraceptive / Trametinib |
| TrametinibEach tablet is 0.5mg trametinib to be taken orally once daily. 0.5mg tablets may be used if a dose reduction is required. | Drug | Oral Contraceptive / Trametinib |
| Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol)Combined oral contraceptive to be taken orally once daily. | Drug | Oral Contraceptive / Trametinib |
Primary outcome
Pharmacokinetics parameter: AUCtau of NE and EE alone and in combination with trametinib
Time frame: 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
Time frame: 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
Time frame: 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: Tmax of NE and EE alone and incombination with trametinib
Time frame: 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.
4 secondary outcomes
Pharmacokinetics parameter: AUClast of M5
Time frame: Day 21 and 22
Pharmacokinetics parameter: AUCtau of M5
Time frame: Day 21 and 22
Pharmacokinetics parameter: Cmax of M5
Time frame: Day 21 and 22
Pharmacokinetics parameter: Tmax of M5
Time frame: Day 21 and 22
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2022.
- Results for CTMT212X2102 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trametinib and Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol) in people with Solid Tumors, run by Novartis Pharmaceuticals at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Belgium, Netherlands, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics parameter: AUCtau of NE and EE alone and in combination with trametinib (time frame: Day 5 and 6 and 21 and 22). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2022; AzTrials last refreshed its copy on 6 Nov 2026.