Non Small Cell Lung CancerPhase 1NCT01147211
Dose Defining Study For MK-2206 Combined With Gefitinib In Non Small Cell Lung Cancer (NSCLC)
A Phase 1 study testing MK2206 in people with Non Small Cell Lung Cancer, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
This is a phase I study of MK2206 (an AKT inhibitor)and gefitinib in nonsmall cell lung cancer patients who failed prior chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). The patient population is enriched for EGFR mutations. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- MK2206
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteTaiwan
- Study dates
- Sep 2010to Dec 2013
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically-confirmed locally advanced or metastatic NSCLC who have received EGFR inhibitors (such as gefitinib, erlotinib) for at least 3 months and progressed and also received at least one line of platinum-based chemotherapy. In the MTD expansion cohort, patients must have documented progression on gefitinib, erlotinib, afatinib(BIBW2992) or PF299804 within 4 weeks of starting gefitinib and MK2206 treatment. There should be no anticancer treatment between above mentioned treatment and protocol treatment.
- Patient is male or female and ≥ 20 years of age on the day of signing informed consent.
- Patient must have performance status ≤ 2 on the ECOG Performance Scale.
- Patient must have adequate organ function
- Female patient of childbearing potential has a negative serum or urine pregnancy test β-hCG within 72 hours prior to receiving the first dose of study medication.
- Patient have completed any targeted therapy (excluding gefitinib, erlotinib or any small molecule EGFR tyrosine kinase inhibitors ), any chemotherapy regimens and therapeutic radiation for a minimum of 30 days prior to starting of treatment, and palliative radiotherapy covering less than 30% bone marrow for a minimum 14 days prior to starting of treatment.
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- Prior usage of BIBW2992 are allowed if patient failed on BIBW2992 over 3-month therapy.
- Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent.
- Patient is able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis.
Who cannot join
- Patient who has had chemotherapy, radiotherapy, biological therapy, or BIBW2992 (except gefitinib, erlotinib) within 30 days (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or 5x half-life, whichever is longer, prior to starting of treatment, or who has not recovered from the adverse events due to previous agents administered more than 30 days prior to Study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1.
- Patients who has had major surgery within 4 weeks prior to starting of treatment or expect major surgery in the study duration.
- Patient is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5x half-life from prior agents, whichever is longer, of Day 1 of this study.
- Patient has known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids.
- Patient with a primary central nervous system tumor.
- Patient has known hypersensitivity to the components of study drug or its analogs.
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- Patient has a history or current evidence of heart disease.
- Patient with evidence of clinically significant bradycardia (HR < 50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2), or patients taking non-dihydropyridine calcium channel blockers, or digoxin.
- Patient with uncontrolled hypertension (i.e. ≥160/90 mHg). Patients who are controlled on antihypertensive medication will be allowed to enter the study.
- Patient at significant risk for hypokalemia (eg. patients on high dose diuretics, or with recurrent diarrhea)
- Patient is a known diabetic patient
- Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
- Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
- Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
- Patient is known to be Human Immunodeficiency Virus (HIV)-positive
- Patient currently has active Hepatitis.
- Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
- Patient is receiving treatment with oral corticosteroids (note: inhaled corticosteroids or premedication for chemotherapy are permitted).
- Patient is using a potent CYP3A4 inhibitor or inducer (See Appendix 6.2) for a list of potent CYP3A4 inhibitors or inducers). Patients who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is longer) prior to the first dose MK-2206.
- Patient who has received gefitinib and discontinued due to gefitinib-related toxicity.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Dose Defining Study For MK-2206 Combined With Gefitinib In NSCLC Population Enriched With EGFR Mutation
This is a phase I study of MK2206 (an AKT inhibitor)and gefitinib in nonsmall cell lung cancer patients who failed prior chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). The patient population is enriched for EGFR mutations.
The purpose of this study is to determine whether it is safe to administered MK-2206 in combination with gefitinib in adult patients with locally advanced or metastatic non-small cell lung cancer. The second purpose of this study is to define the MTD (Maximum Tolerated Dose) of MK-2206 when combined with gefitinib.
A standard 3-3 dose escalation scheme of MK-2206 with fix dose gefitinib is used in this study.
Read the detailed description
Preclinical data from communication with Merck clinical and pre-clinical group support the application of MK2206 and an EGFR-TKI, and the synergistic effect of this combination. This proposed study is a phase I dose defining study to define the MTD (Maximum Tolerated Dose) of MK-2206 when combined with gefitinib.
MK-2206 is a potent, orally active, allosteric inhibitor of human AKT1, AKT2, and AKT3 with preclinical anti-tumor activity.
This is a Phase I, single-center, open-label, non-randomized, dose-escalation study in patients with locally advanced or metastatic NSCLC. Patients who previously failed and progressed through EGFR inhibitor such as erlotinib or gefitinib and up to one line of chemotherapy will be enrolled into the study. Patients will be administered with oral MK-2206 and a standard dose of EGFR inhibitor gefitinib.
This study will be conducted in three cohorts to identify a recommended Phase II dose (RP2D) of MK-2206 in combination with standard dose of gefitinib (250 mg QD). Cohorts of 3 patients will be enrolled sequentially on escalating doses of MK-2206 administered in combination with a standard dose of gefitinib. Patients will advance doses of MK2206 if 0/3 patients or 0-1/6 develop DLT (Dose-Limiting Toxicity). If 1/3 patient develops DLT, the cohort will be expanded to 6. If 2/6 patients developed DLT, the dose will be de-escalate to 90 mg Qwk. The highest dose cohort with 0-1/6 with DLT will be deemed as MTD and used as cohort expansion for a total of 15 patients.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- MK2206
- Keywords
- dose defining, MK-2206, NSCLC With EGFR Mutation, NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK2206Drug
MK-2206 will be administered orally in a starting dose level of 135 mg on a schedule of Qwk in repeating 3-week treatment cycles in combination with gefitinib in continuous 21-day cycles for the duration of the study
| Study group | Role | What they receive |
|---|---|---|
| MK2206 in combination with Gefitinib | Experimental | MK-2206 will be administered orally in a starting dose level of 135 mg on a schedule of Qwk in repeating 3-week treatment cycles in combination with gefitinib in continuous 21-day cycles for the duration of the study Receives: Drug: MK2206 |
What is being measured
The primary outcome is the main question the study is designed to answer.
to provide safety assessment and define dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of MK-2206 in combination with gefitinib in NSCLC
Measured: 21 days
Secondary outcomes (1)
To explore the anti-tumor activity and to assess the pharmacokinetic profile of MK-2206 in combination with gefitinib.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2010 (estimated)
- Study startSep 2010
- Primary completionJul 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chih-Hsin Yang, MD, Ph.D, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01147211
- Sponsor's protocol ID
- 201001017M
- Status last verified
- Apr 2013
- First submitted
- 17 Jun 2010
- Last updated
- 3 May 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Defining Study For MK-2206 Combined With Gefitinib In NSCLC Population Enriched With EGFR Mutation
- ClinicalTrials.gov ID
- NCT01147211
- Acronym / sponsor ID
- 201001017M
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- dose defining, MK-2206, NSCLC With EGFR Mutation, NSCLC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Jul 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 22 Jun 2010 (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.
This is a phase I study of MK2206 (an AKT inhibitor)and gefitinib in nonsmall cell lung cancer patients who failed prior chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). The patient population is enriched for EGFR mutations.
The purpose of this study is to determine whether it is safe to administered MK-2206 in combination with gefitinib in adult patients with locally advanced or metastatic non-small cell lung cancer. The second purpose of this study is to define the MTD (Maximum Tolerated Dose) of MK-2206 when combined with gefitinib.
A standard 3-3 dose escalation scheme of MK-2206 with fix dose gefitinib is used in this study.
Detailed description
Preclinical data from communication with Merck clinical and pre-clinical group support the application of MK2206 and an EGFR-TKI, and the synergistic effect of this combination. This proposed study is a phase I dose defining study to define the MTD (Maximum Tolerated Dose) of MK-2206 when combined with gefitinib.
MK-2206 is a potent, orally active, allosteric inhibitor of human AKT1, AKT2, and AKT3 with preclinical anti-tumor activity.
This is a Phase I, single-center, open-label, non-randomized, dose-escalation study in patients with locally advanced or metastatic NSCLC. Patients who previously failed and progressed through EGFR inhibitor such as erlotinib or gefitinib and up to one line of chemotherapy will be enrolled into the study. Patients will be administered with oral MK-2206 and a standard dose of EGFR inhibitor gefitinib.
This study will be conducted in three cohorts to identify a recommended Phase II dose (RP2D) of MK-2206 in combination with standard dose of gefitinib (250 mg QD). Cohorts of 3 patients will be enrolled sequentially on escalating doses of MK-2206 administered in combination with a standard dose of gefitinib. Patients will advance doses of MK2206 if 0/3 patients or 0-1/6 develop DLT (Dose-Limiting Toxicity). If 1/3 patient develops DLT, the cohort will be expanded to 6. If 2/6 patients developed DLT, the dose will be de-escalate to 90 mg Qwk. The highest dose cohort with 0-1/6 with DLT will be deemed as MTD and used as cohort expansion for a total of 15 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MK2206 in combination with Gefitinib | Experimental | Drug: MK2206MK-2206 will be administered orally in a starting dose level of 135 mg on a schedule of Qwk in repeating 3-week treatment cycles in combination with gefitinib in continuous 21-day cycles for the duration of the study |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients must have histologically or cytologically-confirmed locally advanced or metastatic NSCLC who have received EGFR inhibitors (such as gefitinib, erlotinib) for at least 3 months and progressed and also received at least one line of platinum-based chemotherapy. In the MTD expansion cohort, patients must have documented progression on gefitinib, erlotinib, afatinib(BIBW2992) or PF299804 within 4 weeks of starting gefitinib and MK2206 treatment. There should be no anticancer treatment between above mentioned treatment and protocol treatment.
- Patient is male or female and ≥ 20 years of age on the day of signing informed consent.
- Patient must have performance status ≤ 2 on the ECOG Performance Scale.
- Patient must have adequate organ function
- Female patient of childbearing potential has a negative serum or urine pregnancy test β-hCG within 72 hours prior to receiving the first dose of study medication.
Key exclusion criteria (21 listed)
- Patient who has had chemotherapy, radiotherapy, biological therapy, or BIBW2992 (except gefitinib, erlotinib) within 30 days (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or 5x half-life, whichever is longer, prior to starting of treatment, or who has not recovered from the adverse events due to previous agents administered more than 30 days prior to Study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1.
- Patients who has had major surgery within 4 weeks prior to starting of treatment or expect major surgery in the study duration.
- Patient is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5x half-life from prior agents, whichever is longer, of Day 1 of this study.
- Patient has known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids.
- Patient with a primary central nervous system tumor.
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 |
|---|---|---|
| MK2206MK-2206 will be administered orally in a starting dose level of 135 mg on a schedule of Qwk in repeating 3-week treatment cycles in combination with gefitinib in continuous 21-day cycles for the duration of the study | Drug | MK2206 in combination with Gefitinib |
Primary outcome
to provide safety assessment and define dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of MK-2206 in combination with gefitinib in NSCLC
Time frame: 21 days
1 secondary outcome
To explore the anti-tumor activity and to assess the pharmacokinetic profile of MK-2206 in combination with gefitinib.
Time frame: 21 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2013.
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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.
Chih-Hsin Yang, MD, Ph.D principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK2206 in people with Non Small Cell Lung Cancer, run by National Taiwan University Hospital at 1 site in Taiwan.
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 9 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 3 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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?
Results are not available in the source record.
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?
to provide safety assessment and define dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of MK-2206 in combination with gefitinib in NSCLC (time frame: 21 days). 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 3 May 2013.