Non-small Cell Lung Cancer (NSCLC)Phase 1/2NCT02025114
Selumetinib in Combination With Gefitinib in NSCLC Patients
A Phase 1/2 study testing selumetinib in people with Non-small Cell Lung Cancer (NSCLC), run by National Taiwan University Hospital at 3 sites in Taiwan.
Trial summary
This is an open-label, non-randomized, multicenter phase Ib/II study, which is composed of a phase Ib dose escalation part and a phase II dose expansion part. Patients will receive selumetinib in combination with gefitinib 250mg daily. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- selumetinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 3 sitesTaiwan
- Study dates
- Sep 2014to 8 Mar 2018
- Phase
- Phase 1/2
- 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
- Written informed consent obtained prior to any screening procedures.
- ≥20 years of age.
- Must have discontinued any previous anti-cancer and investigational therapy (excluding EGFR TKI) for at least 28 days or radiotherapy ≥14 days before study treatment administration, and must have recovered to Grade 1 from the adverse effects of such treatment before starting study treatment.
- Life expectancy ≥3months.
- ECOG performance status: 0-1.
- Female patients of child-bearing potential should have a negative pregnancy test.
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- Required baseline laboratory status:
- Hemoglobin>9g/dL. (2) Platelet count≥100x109/L. (3) Absolute neutrophil count (ANC)≥1.5x109/L without growth factor support. (4) Total bilirubin 1.5x upper limit of normal (ULN). (5) AST/SGOT and/or ALT/SGPT 2.5x ULN. (6) Serum creatinine clearance >50 ml/min, by either Cockcroft-Gault formula or by 24-hour urine collection analysis.
- 8. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
- 9. In phase Ib part, lung cancer patients with disease progression after EGFR TKI and at least one line of chemotherapy. If less than 70 years of age, a platinum-based regimen must be included.
- 10. In phase II part, patients must be willing to perform a re-biopsy of the tumor at the time of study entrance and meet definition of acquired resistance criteria of Jackman's as follows:
- Previous treatment with EGFR TKI (gefitinib, erlotinib, afatinib, dacomitinib, AZD9291, or any EGFR TKI under investigation).
- Either or both of the followings:
- A tumor harboring an EGFR mutation known to be associated with drug sensitivity (ie, exon 19 deletion , L858R, L861Q, G719X etc.).
- Objectively clinical benefit from treatment with EGFR TKI as defined by either: Documented partial or complete response (RECIST or WHO) or Significant and durable(≥ 6months) clinical benefit (stable disease as defined by RECIST or WHO) after initiation of EGFR TKI.
- Systemic progression of disease (RECIST or WHO) while on continuous treatment with EGFR TKI within the last 30 days.
- No intervening systemic therapy between cessation of EGFR TKI and initiation the study treatment.
Who cannot join
- Unable or unwilling to swallow capsules once or twice daily.
- Patients who had discontinued previous gefitinib treatment due to intolerance of side effects (such as diarrhea ≥CTCAE Grade 2, intolerable skin rash, ILD or AST/ALT elevation ≥ CTCAE Grade 3).
- Previous treatment of MEK, Ras, or Raf inhibitors or history of hypersensitivity to selumetinib, or any excipient agents.
- Symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control the CNS condition.
- Radiation therapy within 4 weeks prior to the first dose of study drug or limited field radiotherapy within 2 weeks prior to the start of study treatment. Any persistent side effect of prior radiotherapy must be resolved to Grade 1 prior to the first dose of study treatment.
- Any unresolved toxicity from previous anticancer therapy > Grade 1.
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- Currently receiving any prohibited medications including vitamins supplements, and herbal supplements. Refer to Table 6.5 for a list of excluded medication.
- Unable to undergo an MRI or contrast CT procedures.
- Active HBV or HCV infection, HBV carrier can be enrolled if HBV DNA titer is low under antiviral treatment.
- Known history of HIV seropositivity. HIV testing is not required as part of this study.
- Undergone a bone marrow or solid organ transplant.
- Another malignancy diagnosed or treated within 5 years, except carcinoma in situ or skin cancer.
- Major surgery within 4 weeks prior to initiating study treatment, excluding the placement of vascular access.
- Cardiac conditions as follows:
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- Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy).
- Left ventricular ejection fraction <55% measured by echocardiography.
- Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest.
- Symptomatic heart failure (NYHA grade II-IV), see Appendix A.
- Prior or current cardiomyopathy.
- Severe valvular heart disease.
- Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), see Appendix A.
- Acute coronary syndrome within 6 months prior to starting treatment". 15. Ophthalmological conditions as follows:
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- Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure).
- Current or past history of central serous retinopathy or retinal vein occlusion.
- 16. Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment, pre-existing idiopathic pulmonary fibrosis or any evidence of clinically active interstitial lung disease.
- 17. Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>5mIU/mL).
- 18. Women of child-bearing potential, defined as all women physically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 30 more days after stopping study drug.
- 19. Women are considered post-menopausal and not of child baring potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- 20. Sexually active males must use a condom during intercourse while taking the drug and for 30 more days after stopping study drug and should not father a child in this period. A condom is required to be used also by a vasectomized men in order to prevent delivery of the drug via seminal fluid.
- 21. Any other condition that would, in the Investigator's judgment, contraindicate patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, unable to swallow medication, social/psychological issues, etc.
Trial locations and contacts
3 sites in 1 country.
Taiwan3 sites
National Cheng Kung University Hospital
Tainan, 70403
Department of Oncology, National Taiwan University Hospital
Taipei, 100
Taipei Veterans General Hospital
Taipei, 11217
About this study
Official title: A Phase IB/II, Open Label, Multicenter Study of Selumetinib Administered Orally in Combination With Gefitinib in Patients With EGFR-mutated Non-small Cell Lung Cancer Who Have Developed Acquired Resistance of EGFR Inhibitor Treatment
This is an open-label, non-randomized, multicenter phase Ib/II study, which is composed of a phase Ib dose escalation part and a phase II dose expansion part. Patients will receive selumetinib in combination with gefitinib 250mg daily. This study will enroll EGFR-mutated NSCLC patients who have developed acquired resistance to EGFR TKI treatment.
Read the detailed description
he primary objective of the dose escalation part is to determine the MTD and/or RP2D of selumetinib in combination with gefinitib. Once MTD and/or RP2D has been determined in the phase Ib dose escalation phase, study drug selumetinib with combination of 250mg QD dose of gefitinib will be further evaluated in a phase II dose expansion phase of the study. The purpose of the dose expansion phase is to evaluate the efficacy of selumetinib in combination of gefitinib and to further characterize the safety, and tolerability of the combination.
20 patients will be required in the phase II period. In the expansion phase, 10 patients with T790M and 10 patients without T790M will be enrolled. It is assumed that 20% response rate is the target of clinical interest. If the true response rate is 20%, the probability of observing no responses in a random sample of 10 patients is 0.107. The false negative rate for detecting a true 20% response rate in each cohort is approximately 10%. Each cohort will be enrolled 10 patients to evaluate the efficacy; therefore 20 patients will be enrolled in dose expansion part. Patients treated at the MTD and/or RP2D during the phase Ib will be considered as part of the required number of patients in the phase II. Patients at the MTD or RP2D cannot contribute to the 20 patients require for phase II part.
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Being tested
- selumetinib
- Keywords
- NSCLC, EGFR mutation
- 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.
selumetinibDrug
The starting dose of selumetinib in combination with the standard dose of gefitinib (250mg QD) on a continuous dosing schedule will be 50mg QD. Total 3 doses of selumetinib will be tested (50mg QD, 50mg BID and 75mg BID).
| Study group | Role | What they receive |
|---|---|---|
| Capsule | Experimental | The starting dose of selumetinib in combination with the standard dose of gefitinib (250mg QD) on a continuous dosing schedule will be 50mg QD. Total 3 doses of selumetinib will be tested (50mg QD, 50mg BID and 75mg BID). Receives: Drug: selumetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the MTD and/or RP2D
Frequency and characteristics of DLTs to the selumetinib and gefitinib combination using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0. (an expected average of 18 weeks) If one patient experiences a DLT in a group of 3 or more evaluable patients, then the cohort will be expanded to include 6 evaluable patients. If only one DLT is observed in the complete cohort of 6 evaluable patients, then dose escalation may occur.
Measured: an expected average of 18 weeks
Secondary outcomes (1)
Overall Response Rate (ORR)
to estimate overall clinical activity of selumetinib combined with gefitinib in EGFR-mutated NSCLC patients who have acquired resistance to EGFR TKIs
Measured: Patients will be followed up for 2 years(post disease progression)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2013 (estimated)
- Study startSep 2014
- Primary completion8 Mar 2018
- Study completion8 Mar 2018
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 Cancer (NSCLC)Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chih-Hsin Yang, MD, PhD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02025114
- Sponsor's protocol ID
- 201312070MIPC
- Status last verified
- Jul 2018
- First submitted
- 24 Dec 2013
- Last updated
- 10 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB/II, Open Label, Multicenter Study of Selumetinib Administered Orally in Combination With Gefitinib in Patients With EGFR-mutated Non-small Cell Lung Cancer Who Have Developed Acquired Resistance of EGFR Inhibitor Treatment
- ClinicalTrials.gov ID
- NCT02025114
- Acronym / sponsor ID
- 201312070MIPC
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Keywords
- NSCLC, EGFR mutation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- 8 Mar 2018 (actual)
- Study completion
- 8 Mar 2018 (actual)
- First posted
- 31 Dec 2013 (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 an open-label, non-randomized, multicenter phase Ib/II study, which is composed of a phase Ib dose escalation part and a phase II dose expansion part. Patients will receive selumetinib in combination with gefitinib 250mg daily. This study will enroll EGFR-mutated NSCLC patients who have developed acquired resistance to EGFR TKI treatment.
Detailed description
he primary objective of the dose escalation part is to determine the MTD and/or RP2D of selumetinib in combination with gefinitib. Once MTD and/or RP2D has been determined in the phase Ib dose escalation phase, study drug selumetinib with combination of 250mg QD dose of gefitinib will be further evaluated in a phase II dose expansion phase of the study. The purpose of the dose expansion phase is to evaluate the efficacy of selumetinib in combination of gefitinib and to further characterize the safety, and tolerability of the combination.
20 patients will be required in the phase II period. In the expansion phase, 10 patients with T790M and 10 patients without T790M will be enrolled. It is assumed that 20% response rate is the target of clinical interest. If the true response rate is 20%, the probability of observing no responses in a random sample of 10 patients is 0.107. The false negative rate for detecting a true 20% response rate in each cohort is approximately 10%. Each cohort will be enrolled 10 patients to evaluate the efficacy; therefore 20 patients will be enrolled in dose expansion part. Patients treated at the MTD and/or RP2D during the phase Ib will be considered as part of the required number of patients in the phase II. Patients at the MTD or RP2D cannot contribute to the 20 patients require for phase II part.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Capsule | Experimental | Drug: selumetinibThe starting dose of selumetinib in combination with the standard dose of gefitinib (250mg QD) on a continuous dosing schedule will be 50mg QD. Total 3 doses of selumetinib will be tested (50mg QD, 50mg BID and 75mg BID). |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Written informed consent obtained prior to any screening procedures.
- ≥20 years of age.
- Must have discontinued any previous anti-cancer and investigational therapy (excluding EGFR TKI) for at least 28 days or radiotherapy ≥14 days before study treatment administration, and must have recovered to Grade 1 from the adverse effects of such treatment before starting study treatment.
- Life expectancy ≥3months.
- ECOG performance status: 0-1.
Key exclusion criteria (32 listed)
- <!-- -->
- <!-- -->
- 16. Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment, pre-existing idiopathic pulmonary fibrosis or any evidence of clinically active interstitial lung disease.
- 17. Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>5mIU/mL).
- 18. Women of child-bearing potential, defined as all women physically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 30 more days after stopping study drug.
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 |
|---|---|---|
| selumetinibThe starting dose of selumetinib in combination with the standard dose of gefitinib (250mg QD) on a continuous dosing schedule will be 50mg QD. Total 3 doses of selumetinib will be tested (50mg QD, 50mg BID and 75mg BID). | Drug | Capsule |
Primary outcome
To determine the MTD and/or RP2D
Time frame: an expected average of 18 weeks
Frequency and characteristics of DLTs to the selumetinib and gefitinib combination using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0. (an expected average of 18 weeks) If one patient experiences a DLT in a group of 3 or more evaluable patients, then the cohort will be expanded to include 6 evaluable patients. If only one DLT is observed in the complete cohort of 6 evaluable patients, then dose escalation may occur.
1 secondary outcome
Overall Response Rate (ORR)
Time frame: Patients will be followed up for 2 years(post disease progression)
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 10 Jul 2018.
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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, PhD principal investigator
National Taiwan University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing selumetinib in people with Non-small Cell Lung Cancer (NSCLC), run by National Taiwan University Hospital at 3 sites 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 17 inclusion and 32 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 10 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
To determine the MTD and/or RP2D (time frame: an expected average of 18 weeks). 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 10 Jul 2018.