Non-Small Cell Lung CancerPhase 1/2NCT02403271
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors
A Phase 1/2 study testing Ibrutinib and Durvalumab in people with Non-Small Cell Lung Cancer and Breast Cancer, run by Pharmacyclics LLC. at 17 sites in United States.
Trial summary
This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, Breast Cancer, Pancreatic Cancer
- What is being tested?
- Ibrutinib and Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 17 sitesUnited States
- Study dates
- Mar 2015to Aug 2017
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed: Non-small cell lung cancer (NSCLC, adenocarcinoma or squamous-cell carcinoma), Breast Cancer (HER2 positive or triple negative), Pancreatic Cancer (adenocarcinoma)
- Relapsed or refractory disease (Stage III or IV): NSCLC or pancreatic cancer must have failed at least 1 prior treatment. Breast cancer must have failed at least 2 prior treatments.
- Measurable lesion by RECIST 1.1
- Adequate hematologic function:
- ANC >1500 cells/mm3
- Platelet count >100,000 cells/mm3
Show all 12Show fewer
- HGB >9.0 g/dL
- Adequate hepatic and renal function:
- AST and ALT ≤2.5 x ULN for subjects without liver metastases and ≤3.5 x ULN for subjects with liver metastases
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- Creatinine ≤2.0 x ULN and Creatinine Clearance ≥40 mL/min (Cockcroft-Gault or 24-hour creatinine clearance collection)
- PT/INR <1.5 x ULN and PTT/ aPTT <1.5 x ULN
Who cannot join
- Mixed small cell and NSCLC histology
- A history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least 14 days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least 90 days prior to enrollment.
- Anti-tumor therapy within 21 days of study Day 1
- Prior treatment with ibrutinib or other BTK inhibitor anti-CD137 or CTLA-4 antibody. The following are exceptions to this criterion: Subjects previously treated with an anti-PD1, anti-PD-L1, or anti-PD-L2 antibody.
- History of allogeneic organ transplant
- Treatment with a strong cytochrome P450 (CYP) 3A inhibitor
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Study site
Birmingham, Alabama, 35294
Study site
Chicago, Illinois, 60637
Study site
Durham, North Carolina, 27710
Study site
Gainesville, Florida, 32610
Study site
Germantown, Tennessee, 38120
Study site
Hackensack, New Jersey, 07601
Study site
Houston, Texas, 77030
Study site
La Jolla, California, 92093
Study site
Los Angeles, California, 90025
Study site
Los Angeles, California, 90048
Study site
Nashville, Tennessee, 37212
Study site
Orlando, Florida, 32806
Study site
Palo Alto, California, 94305
Study site
Peoria, Illinois, 61615
Study site
San Antonio, Texas, 78229
Study site
San Francisco, California, 94115
Study site
Scottsdale, Arizona, 85258
About this study
Official title: A Multi-Center Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Durvalumab (MEDI4736), in Subjects With Relapsed or Refractory Solid Tumors
This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.
- Conditions
- Non-Small Cell Lung Cancer, Breast Cancer, Pancreatic Cancer
- Being tested
- Ibrutinib, Durvalumab
- Keywords
- Pharmacyclics, PCYC, Ibrutinib, Durvalumab (MEDI4736), Relapsed Refractory Solid Tumor, Non-Small Cell Lung Cancer, NSCLC, Squamous, Squamous NSCLC, Squamous Non-Small Cell Lung Cancer, Immunotherapy, IMBRUVICA®, Tumor Immunotherapy, Anti-PD-L1, Lung Cancer, Breast Cancer, Triple Negative, HER2 Positive, HER2 + Breast Cancer, Pancreatic Cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Breast Neoplasms, Pancreatic Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called PCI-32765
BTK Inhibitor
DurvalumabDrug
Also called MEDI4736
Anti PDL-1
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b | Experimental | In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6+3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma). Receives: Drug: Ibrutinib; Drug: Durvalumab |
| Phase 2 | Experimental | Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results. Receives: Drug: Ibrutinib; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.
Measured: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.
Measured: From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.
Secondary outcomes (7)
Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib
Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.
Measured: 0hr, 1hr, 2hr, and 4hr post-dose
Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib
AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1
Measured: 0hr, 1hr, 2hr, and 4hr post-dose
Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)
Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.
Measured: 60 minutes post-dose (dose administered as an infusion over a 1 hour period)
Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)
Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1
Measured: Pre-dose
Phase 1b: Pharmacodynamics
BTK occupancy
Measured: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)
Measured: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Pharmacodynamics
BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.
Measured: Pre-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionAug 2017
- Study completionAug 2017
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 Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmacyclics LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Isaiah Dimery, Study director, Pharmacyclics LLC.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02403271
- Sponsor's protocol ID
- PCYC-1135-CA
- Status last verified
- Dec 2018
- First submitted
- 27 Feb 2015
- Last updated
- 3 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Durvalumab (MEDI4736), in Subjects With Relapsed or Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT02403271
- Acronym / sponsor ID
- PCYC-1135-CA
- Conditions
- Non-Small Cell Lung Cancer, Breast Cancer, Pancreatic Cancer
- Keywords
- Pharmacyclics, PCYC, Ibrutinib, Durvalumab (MEDI4736), Relapsed Refractory Solid Tumor, Non-Small Cell Lung Cancer, NSCLC, Squamous
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Pharmacyclics LLC.Industry (pharma, biotech, devices)
- Study start
- Mar 2015 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 31 Mar 2015 (estimated)
- Results
- Posted 3 Jan 2019
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 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1b | Experimental | Drug: Ibrutinib, Drug: DurvalumabIn the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6+3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma). |
| Phase 2 | Experimental | Drug: Ibrutinib, Drug: DurvalumabParticipants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Pathologically confirmed: Non-small cell lung cancer (NSCLC, adenocarcinoma or squamous-cell carcinoma), Breast Cancer (HER2 positive or triple negative), Pancreatic Cancer (adenocarcinoma)
- Relapsed or refractory disease (Stage III or IV): NSCLC or pancreatic cancer must have failed at least 1 prior treatment. Breast cancer must have failed at least 2 prior treatments.
- Measurable lesion by RECIST 1.1
- Adequate hematologic function:
- Adequate hepatic and renal function:
Key exclusion criteria (6 listed)
- Mixed small cell and NSCLC histology
- A history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least 14 days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least 90 days prior to enrollment.
- Anti-tumor therapy within 21 days of study Day 1
- Prior treatment with ibrutinib or other BTK inhibitor anti-CD137 or CTLA-4 antibody. The following are exceptions to this criterion: Subjects previously treated with an anti-PD1, anti-PD-L1, or anti-PD-L2 antibody.
- History of allogeneic organ transplant
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 |
|---|---|---|
| IbrutinibAlso: PCI-32765BTK Inhibitor | Drug | Phase 1b, Phase 2 |
| DurvalumabAlso: MEDI4736Anti PDL-1 | Drug | Phase 1b, Phase 2 |
Primary outcome
Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.
Time frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.
Time frame: From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.
7 secondary outcomes
Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib
Time frame: 0hr, 1hr, 2hr, and 4hr post-dose
Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib
Time frame: 0hr, 1hr, 2hr, and 4hr post-dose
Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)
Time frame: 60 minutes post-dose (dose administered as an infusion over a 1 hour period)
Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)
Time frame: Pre-dose
Phase 1b: Pharmacodynamics
Time frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)
Time frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Pharmacodynamics
Time frame: Pre-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 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.
Isaiah Dimery study director
Pharmacyclics LLC.
17 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 Ibrutinib and Durvalumab in people with Non-Small Cell Lung Cancer and Breast Cancer, run by Pharmacyclics LLC. at 17 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 12 inclusion and 6 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 3 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 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 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?
Yes. Results are posted in the registry (first posted 3 Jan 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?
Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose. (time frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.). The study lists 2 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 3 Jan 2019.