Locally Advanced or Metastatic NSCL Cancer Stage IIIB IVPhase 1SELECT-3NCT01809210

Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer

A Phase 1 study testing selumetinib, gemcitabine and cisplatin in people with Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV, run by AstraZeneca at 4 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
What is being tested?: selumetinib, gemcitabine and cisplatin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 55 participants
Where: 4 sitesUnited Kingdom
Study dates: 4 Apr 2013to 4 Jan 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provision of signed, written and dated consent prior to any study specific procedures
Male or female, aged 18 years or older
Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information

Who cannot join

Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection

Trial locations and contacts

4 sites in 1 country.

United Kingdom4 sites

Research Site
Glasgow, G12 0YN
Research Site
London, W1G 6AD
Research Site
Manchester, M20 4BX
Research Site
Newcastle upon Tyne, NE7 7DN

Other trials in United Kingdom

About this study

Official title: A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer (NSCLC)

This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity.

This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.

Read the detailed description

A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination with First Line Chemotherapy Regimens in Patients with Non-Small Cell Lung Cancer (NSCLC)

Conditions: Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
Being tested: selumetinib, gemcitabine, cisplatin, carboplatin, pemetrexed
Keywords: MEK1/2 inhibitor,, Non Small Cell Lung Cancer,, metastatic,, first line treatment for Non Small Cell Lung Cancer
Medical subject headings: Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

selumetinibDrug
2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin). If tolerated - next cohort 3 x 25mg capsules bd continuously. if higher doses are explored, required number of capsules will be provided. Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy
gemcitabineDrug
1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle. If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
cisplatinDrug
75 mg/m2 iv on Day 1 of each 21 day cycle. If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
carboplatinDrug
If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle
pemetrexedDrug
Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.

Study groups in NCT01809210
Study group	Role	What they receive
Selumetinib+standard chemotherapy	Experimental	Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin Receives: Drug: selumetinib; Drug: gemcitabine; Drug: cisplatin; Drug: carboplatin; Drug: pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting
Measured: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks

Secondary outcomes (8)

Best Objective Response
The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm
Measured: Screening, week 6 and week 12
Percentage Change From Baseline at 6 Weeks in Target Lesion Size
The percentage change in the sum of the diameters of target lesions
Measured: Week 6
Best Percentage Change From Baseline in Target Lesion Size
The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions
Measured: Screening, week 6 and week 12
Objective Response Rate (ORR)
The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR
Measured: Up until progression or last evaluable assessment in the absence of progression, up to 9 months
AUC (0-tau)
Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)
Measured: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Cmax,ss
Maximum plasma concentration at steady state
Measured: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Tmax,ss
Time to reach maximum plasma concentration at steady state
Measured: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
CL/F
Apparent oral plasma clearance
Measured: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Apr 20134 Jan 2016

First posted12 Mar 2013 (estimated)
Study start4 Apr 2013
Primary completion4 Jan 2016
Study completion4 Jan 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Locally Advanced or Metastatic NSCL Cancer Stage IIIB IVStudies of the same condition, open and under way.
More trials run by AstraZenecaThe 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: 55 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01809210
Sponsor's protocol ID: D1532C00070
Other IDs: EudraCT number: 2012-005202-22
Acronym: SELECT-3
Status last verified: Mar 2018
First submitted: 8 Mar 2013
Last updated: 13 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 13 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer (NSCLC)
ClinicalTrials.gov ID: NCT01809210
Acronym / sponsor ID: SELECT-3 / D1532C00070
Conditions: Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
Keywords: MEK1/2 inhibitor,, Non Small Cell Lung Cancer,, metastatic,, first line treatment for Non Small Cell Lung Cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 55 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 4 Apr 2013 (actual)
Primary completion: 4 Jan 2016 (actual)
Study completion: 4 Jan 2016 (actual)
First posted: 12 Mar 2013 (estimated)
Results: Posted 13 Mar 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Selumetinib+standard chemotherapy	Experimental	Drug: selumetinib, Drug: gemcitabine, Drug: cisplatin, Drug: carboplatin, Drug: pemetrexedSelumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Provision of signed, written and dated consent prior to any study specific procedures
Male or female, aged 18 years or older
Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information

Key exclusion criteria (5 listed)

Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection

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
selumetinib2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin). If tolerated - next cohort 3 x 25mg capsules bd continuously. if higher doses are explored, required number of capsules will be provided. Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy	Drug	Selumetinib+standard chemotherapy
gemcitabine1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle. If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle	Drug	Selumetinib+standard chemotherapy
cisplatin75 mg/m2 iv on Day 1 of each 21 day cycle. If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle	Drug	Selumetinib+standard chemotherapy
carboplatinIf it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle	Drug	Selumetinib+standard chemotherapy
pemetrexedGemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.	Drug	Selumetinib+standard chemotherapy

Primary outcome

Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
Time frame: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting

8 secondary outcomes

Best Objective Response
Time frame: Screening, week 6 and week 12
Percentage Change From Baseline at 6 Weeks in Target Lesion Size
Time frame: Week 6
Best Percentage Change From Baseline in Target Lesion Size
Time frame: Screening, week 6 and week 12
Objective Response Rate (ORR)
Time frame: Up until progression or last evaluable assessment in the absence of progression, up to 9 months
AUC (0-tau)
Time frame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Cmax,ss
Time frame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Tmax,ss
Time frame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
CL/F
Time frame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose

Results and safety

Results posted to the registry on 13 Mar 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1 sel50, Gem, Cis	3	2
Cohort 2 sel50, Gem, Carb	9	8
Cohort 3 sel75, Gem, Cis	7	4
Cohort 4 sel150, Pem, Carb	3	2
Cohort 5 sel75, Pem, Carb	6	4
Cohort 6 sel75, Pem, Cis	15	12
Cohort 7 sel100, Pem, Carb	12	7

Primary outcome: Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib

Time frame: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks. Number. Unit: participants

Measure	Cohort 1 sel50, Gem, Cis n = 3	Cohort 2 sel50, Gem, Carb n = 9	Cohort 3 sel75, Gem, Cis n = 7	Cohort 4 sel150, Pem, Carb n = 3	Cohort 5 sel75, Pem, Carb n = 6	Cohort 6 sel75, Pem, Cis n = 15	Cohort 7 sel100, Pem, Carb n = 12
Evaluable patients	3	7	4	3	6	12	6
Evaluable patients with a DLT Event	0	2	1	0	0	1	1

Population analysed: Safety analysis set - all patients who received at least 1 dose of selumetinib.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events are collected throughout the study, from informed consent until the end of follow-up, which is defined as 28 +/- 7 days after selumetinib is discontinued. Patients were expected to receive up to 6 cycles (18 wks) of chemotherapy.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 sel50, Gem, Cis	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Cohort 2 sel50, Gem, Carb	6 of 9 (66.7%)	9 of 9 (100%)	Not reported
Cohort 3 sel75, Gem, Cis	3 of 7 (42.9%)	7 of 7 (100%)	Not reported
Cohort 4 sel150, Pem, Carb	2 of 3 (66.7%)	3 of 3 (100%)	Not reported
Cohort 5 sel75, Pem, Carb	3 of 6 (50%)	6 of 6 (100%)	Not reported
Cohort 6 sel75, Pem, Cis	9 of 15 (60%)	15 of 15 (100%)	Not reported
Cohort 7 sel100, Pem, Carb	9 of 12 (75%)	12 of 12 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
D1532C00070revisedCSP-2\_RedactedLink provided by the sponsor.

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.

Gabriella Mariani, MD study director

AstraZeneca UK, MSD

Emma Dean, BMEDSCI, BM, BS, PHD principal investigator

The Christie NHS Foundation Trust, UK

Fiona Blackhall, PhD, FRCP principal investigator

The Christie NHS Foundation Trust Clinical Trials Unit; UK

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing selumetinib, gemcitabine and cisplatin in people with Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV, run by AstraZeneca at 4 sites in United Kingdom.

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 5 inclusion and 5 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 13 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in 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?

Yes. Results are posted in the registry (first posted 13 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib (time frame: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01809210.

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 13 Mar 2018.