Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)Phase 2NCT02179671
Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
A Phase 2 study testing Gefitinib, AZD9291 and Selumetinib+Docetaxel in people with Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV), run by AstraZeneca at 10 sites in United States.
Trial summary
Primary objective: To assess the efficacy of various sequences of either a small molecule or an IMT (IMT-A) followed by a IMT-B (MEDI4736) . Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)
- What is being tested?
- Gefitinib, AZD9291 and Selumetinib+Docetaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 10 sitesUnited States
- Study dates
- 25 Jul 2014to 11 Jun 2016
- Phase
- Phase 2
- 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 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of archived tumor tissue sample and mandatory tissue biopsy
- Patients must have either histologically or cytologically documented NSCLC who present with locally advanced or metastatic stage IIIB-IV disease
- Life expectancy ≥12 weeks
- Patients must have measurable disease and at least 1 lesion not previously irradiated
- World Health Organization (WHO) performance status of 0 or 1
Who cannot join
- Mixed small cell and NSCLC histology
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Research Site
Ashland, Kentucky, 41101
Research Site
Augusta, Georgia, 30912
Research Site
Goodyear, Arizona, 85338
Research Site
Huntersville, North Carolina, 28078
Research Site
Marietta, Georgia, 30060
Research Site
Mineola, New York, 11501
Research Site
Spokane, Washington, 99208-1129
Research Site
St Louis, Missouri, 63110
Research Site
Tacoma, Washington, 98405
Research Site
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase IIa, Open-Label, Multi-Center, Multi-Cohort, Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)
Primary objective: To assess the efficacy of various sequences of either a small molecule or an IMT (IMT-A) followed by a IMT-B (MEDI4736) .
Read the detailed description
This is a multi-arm, multi-cohort, Phase IIa, open-label study of selected small molecules (gefitinib, AZD9291, or selumetinib + docetaxel) or 1st IMT (hereafter referred to as IMT-A; tremelimumab) followed by sequential switch to a 2nd IMT (hereafter referred to as IMT-B; MEDI4736) in locally advanced or metastatic NSCLC (Stage IIIB-IV). Patients will be enrolled concurrently into multiple cohorts.
- Being tested
- Gefitinib, AZD9291, Selumetinib+Docetaxel, Tremelimumab
- Keywords
- Lung cancer; NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GefitinibDrug
Gefitinib once daily followed by MEDI4736
AZD9291Drug
AZD9291 once daily followed by MEDI4736
Selumetinib+DocetaxelDrug
Selumetinib twice daily + docetaxel, followed by MEDI4736
TremelimumabDrug
Tremelimumab every 4 weeks followed by MEDI4736
| Study group | Role | What they receive |
|---|---|---|
| Gefitinib with a Seq. Switch to a MEDI4736 | Experimental | Gefitinib once daily followed by MEDI4736 Receives: Drug: Gefitinib |
| AZD9291 with a Seq. Switch to a MEDI4736 | Experimental | AZD9291 once daily followed by MEDI4736 Receives: Drug: AZD9291 |
| Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736 | Experimental | Selumetinib twice daily + docetaxel, followed by MEDI4736 Receives: Drug: Selumetinib+Docetaxel |
| Tremelimumab with a Seq. Switch to a MEDI4736 | Experimental | Tremelimumab every 4 weeks followed by MEDI4736 Receives: Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed Complete Response (CR) Rate
To assess the efficacy of various sequences. CR (per RECIST 1.1 as assessed by the local/site Investigator) is defined as the disappearance of all target and non-target lesions. Confirmed complete response rate (CR rate) is defined as the number (%) of patients with a confirmed overall response of CR and was based on the evaluable analysis set.
Measured: Up to 2 years
Secondary outcomes (4)
Objective Response Rate (ORR)
To further assess the efficacy of various sequences. Objective response rate (ORR; per RECIST 1.1 as assessed by the site Investigator) is defined as the number (%) of patients with a confirmed overall response of CR or PR and was based on the evaluable analysis set. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 2 years
Progression-free Survival
Progression-free survival (per RECIST 1.1 as assessed by Investigator) is defined as the date of 1st dose of MEDI4736 until the date of objective disease progression or death. Progression of disease (PD) At least a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Up to 2 years
Duration of Response
Duration of response (DoR; per RECIST 1.1 as assessed by the site Investigator) will be defined as the time from the date of 1st documented response (which is subsequently confirmed) until the 1st date of documented progression or death in the absence of disease progression.
Measured: Within 12 months
Overall Survival
To assess the efficacy of various sequences. In survival follow up at data cut off.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2014 (estimated)
- Study start25 Jul 2014
- Primary completion11 Jun 2016
- Study completion11 Jun 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 Non-Small-Cell Lung Cancer (Stage IIIB-IV)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Responsible party
- Sponsor
- Investigators
- Samir N. Khleif, MD, Principal investigator, International Coordinating Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02179671
- Sponsor's protocol ID
- D4191C00011
- Status last verified
- Aug 2019
- First submitted
- 30 Jun 2014
- Last updated
- 2 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa, Open-Label, Multi-Center, Multi-Cohort, Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)
- ClinicalTrials.gov ID
- NCT02179671
- Acronym / sponsor ID
- D4191C00011
- Keywords
- Lung cancer; NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Study start
- 25 Jul 2014 (actual)
- Primary completion
- 11 Jun 2016 (actual)
- Study completion
- 11 Jun 2016 (actual)
- First posted
- 2 Jul 2014 (estimated)
- Results
- Posted 2 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary objective: To assess the efficacy of various sequences of either a small molecule or an IMT (IMT-A) followed by a IMT-B (MEDI4736) .
Detailed description
This is a multi-arm, multi-cohort, Phase IIa, open-label study of selected small molecules (gefitinib, AZD9291, or selumetinib + docetaxel) or 1st IMT (hereafter referred to as IMT-A; tremelimumab) followed by sequential switch to a 2nd IMT (hereafter referred to as IMT-B; MEDI4736) in locally advanced or metastatic NSCLC (Stage IIIB-IV). Patients will be enrolled concurrently into multiple cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Gefitinib with a Seq. Switch to a MEDI4736 | Experimental | Drug: GefitinibGefitinib once daily followed by MEDI4736 |
| AZD9291 with a Seq. Switch to a MEDI4736 | Experimental | Drug: AZD9291AZD9291 once daily followed by MEDI4736 |
| Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736 | Experimental | Drug: Selumetinib+DocetaxelSelumetinib twice daily + docetaxel, followed by MEDI4736 |
| Tremelimumab with a Seq. Switch to a MEDI4736 | Experimental | Drug: TremelimumabTremelimumab every 4 weeks followed by MEDI4736 |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Provision of archived tumor tissue sample and mandatory tissue biopsy
- Patients must have either histologically or cytologically documented NSCLC who present with locally advanced or metastatic stage IIIB-IV disease
- Life expectancy ≥12 weeks
- Patients must have measurable disease and at least 1 lesion not previously irradiated
- World Health Organization (WHO) performance status of 0 or 1
Key exclusion criteria (2 listed)
- Mixed small cell and NSCLC histology
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
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 |
|---|---|---|
| GefitinibGefitinib once daily followed by MEDI4736 | Drug | Gefitinib with a Seq. Switch to a MEDI4736 |
| AZD9291AZD9291 once daily followed by MEDI4736 | Drug | AZD9291 with a Seq. Switch to a MEDI4736 |
| Selumetinib+DocetaxelSelumetinib twice daily + docetaxel, followed by MEDI4736 | Drug | Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736 |
| TremelimumabTremelimumab every 4 weeks followed by MEDI4736 | Drug | Tremelimumab with a Seq. Switch to a MEDI4736 |
Primary outcome
Confirmed Complete Response (CR) Rate
Time frame: Up to 2 years
To assess the efficacy of various sequences. CR (per RECIST 1.1 as assessed by the local/site Investigator) is defined as the disappearance of all target and non-target lesions. Confirmed complete response rate (CR rate) is defined as the number (%) of patients with a confirmed overall response of CR and was based on the evaluable analysis set.
4 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to 2 years
Progression-free Survival
Time frame: Up to 2 years
Duration of Response
Time frame: Within 12 months
Overall Survival
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Samir N. Khleif, MD principal investigator
International Coordinating Investigator
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gefitinib, AZD9291 and Selumetinib+Docetaxel in people with Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV), run by AstraZeneca at 10 sites in United States.
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 2 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 2 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. 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 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?
Yes. Results are posted in the registry (first posted 2 Aug 2019). 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?
Confirmed Complete Response (CR) Rate (time frame: Up to 2 years). 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 2 Aug 2019.