Lung CancerPhase 1/2URCOH-PMS-001NCT02733250
Pembrolizumab With Nab-Paclitaxel in Non-Small Cell Lung Cancer
A Phase 1/2 study testing Pembrolizumab and Nab-Paclitaxel in people with Lung Cancer, run by Centre hospitalier de l'Université de Montréal (CHUM) at 2 sites in Canada.
Trial summary
The purpose of this study is to determine the optimal dose of nab-paclitaxel to be safely administered in combination with pembrolizumab in patients with advanced inoperable non-small cell lung cancer. The study is also aimed at evaluating the efficacy of the combination therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Pembrolizumab and Nab-Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesCanada
- Study dates
- 13 Mar 2017to 13 Dec 2019
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Have unresectable stage III (not eligible to curative-intent chemo-radiotherapy) or stage IV non-small cell lung cancer (NSCLC) according to the Clarification of Malignant Tumours (TNM) staging system for lung cancer (7th edition).
- Patients must be willing to undergo a biopsy procedure before the start of treatment unless these two conditions are met: 1) the biopsy must have been conducted after progression or intolerance to systemic first-line treatment as stated in criteria 7 and; 2) all the planned correlative analyses can be conducted on the available tissue.
- Have measurable/evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Have an Eastern Cooperative Oncology Group (ECOG) of 0 or 1.
Who cannot join
- Has a known epidermal growth factor receptor (EGFR) sensitizing (activating) mutation and/or anaplastic lymphoma kinase (ALK) translocation.
- Has an unknown EGFR and ALK status.
- Has received prior therapy with paclitaxel or docetaxel for NSCLC.
- Has received systemic steroid therapy within three days prior to the first dose of study treatment or receiving any other form of systemic immunosuppressive medication.
- Has a history of allogeneic tissue/solid organ transplant.
- Has prior systemic cytotoxic chemotherapy, antineoplastic biological therapy, major surgery within 3 weeks of the first dose of study drug; received prior tyrosine kinase inhibitor therapy or completed palliative radiotherapy within 7 days of the first dose of study drug.
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- Has an active infection requiring systemic therapy.
- Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), including pembrolizumab, anti-programmed cell death protein ligand 1 (anti-PD-L1), anti-programmed cell death protein ligand 2 (anti-PD-L2), anti-tumor necrosis factor (CD137), or anticytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug targeting immune checkpoint pathways).
- Has had any other malignancy within 5 years prior to the start of therapy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., expected 5-year overall survival (OS) > 90%).
- Has known active central nervous system (CNS) metastases or leptomeningeal involvement.
- Has active autoimmune disease (or documented history), or a syndrome that requires systemic corticosteroids or immunosuppressive agents (patients with auto-immune thyroid disease, vitiligo or well controlled type 1 diabetes mellitus are eligible).
- Has known history or active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- Women of childbearing potential who is unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Centre hospitalier de l'université de Montréal (CHUM)
Montreal, Quebec, H2X 3E4
Jewish General Hospital
Montreal, Quebec, H3T 1E2
About this study
Official title: A Phase I/II Study of Pembrolizumab in Combination With Nab-Paclitaxel in Patients With Unresectable Stage III or Stage IV Non-Small Cell Lung Carcinoma
The purpose of this study is to determine the optimal dose of nab-paclitaxel to be safely administered in combination with pembrolizumab in patients with advanced inoperable non-small cell lung cancer. The study is also aimed at evaluating the efficacy of the combination therapy.
Read the detailed description
This is a phase 1/2, open-label, proof of concept study of nab-paclitaxel administered in combination with pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC).
Part 1 of the study will assess the dose limiting toxicity (DLT) of nab-paclitaxel in combination with a fixed dose of pembrolizumab (200 mg administered on day 1 of each 21 day cycle). Dose escalation for nab-paclitaxel will be conducted according to the "3+3 design" until the recommended phase 2 dose (RP2D) is determined.
Part 2 of the study will evaluate the administration of pembrolizumab at a dose of 200 mg every 3 weeks in combination with nab-paclitaxel at the RP2D. Determining the RP2D will classify the treatment combination as safe and allow for an expansion of the study population, which will ultimately lead to further assessments of safety and tolerability as well as an evaluation of the anti-tumoral effect of the proposed treatment combination.
Using Simon's optimal 2-stage design for Phase II clinical trials, we determined that a sample size of 36 patients would be adequate to test the proposed hypothesis.
The primary efficacy analysis of overall response rate (ORR) will be interpreted as follows: 1) if less than 9 partial response (PR) or complete response (CR) are recorded, the combination of nab-paclitaxel and pembrolizumab provides less than additive effects and is not likely to be clinically superior compared to pembrolizumab alone based on an ORR assessment; 2) however, if 9 or more PR or CR are recorded, the treatment combination warrants further clinical study. This could take the form of an extended phase II (to reach the 97 patients calculated from the model) or a phase III study.
Treatment will continue until disease progression (as per RECIST 1.1), unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, investigator's noncompliance with trial treatment or procedures requirements, the subject receives 24 months of uninterrupted treatment or 35 administrations of study medication (whichever is later), or administrative reasons.
- Conditions
- Lung Cancer
- Being tested
- Pembrolizumab, Nab-Paclitaxel
- Keywords
- NSCLC, Pembrolizumab, Nab-paclitaxel
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called Keytruda
200mg IV Day 1 of each 21 cycles
Nab-PaclitaxelDrug
Also called Abraxane
100mg/m2 IV Day 1, 8 and 15 of every 21 day cycles
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Nab-Paclitaxel | Other | Phase I will determine the recommended Phase II dose (RP2D) of nab-paclitaxel when given in combination with pembrolizumab. Escalation for nab-paclitaxel will be conducted following a "3+3" design. First cohort of 3 patients will receive nab-paclitaxel on Days 1 and 8 at a dose of 100 mg/m2 intravenous (IV) in combination with pembrolizumab at 200 mg IV every 3 weeks. If no dose limiting toxicities (DLT) occur, the dose of nab-paclitaxel will be escalated to 100 mg/m2 on Days 1, 8 and 15 every 3 weeks. The dose of pembrolizumab will remain the same. If no DLTs occur, dose level 2 will be defined as the RP2D. In the Phase II, pembrolizumab will be administered at 200 mg IV every 3 weeks and nab-paclitaxel will be administered at the RP2D. Receives: Biological: Pembrolizumab; Drug: Nab-Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of nab-paclitaxel in combination with pembrolizumab as measured by incidence of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities.
Safety analysis will be based on subjects who experienced toxicities as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Safety will be assessed by quantifying the toxicities and grades experienced by subjects who received at least one dose of pembrolizumab and nab-paclitaxel, including serious adverse events (SAEs) and event of clinical interest (ECIs).
Measured: Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose.
Objective Response Rate (ORR)
Defined as the proportion of patients with best overall response or either complete response or partial response, which will be recorded based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or the Immune related response criteria (irRC).
Measured: up to 56 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2016 (estimated)
- Study start13 Mar 2017
- Primary completion13 Apr 2019
- Study completion13 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The 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
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Merck Canada Inc., Celgene, Jewish General Hospital
- Responsible party
- Sponsor
- Investigators
- Normand Blais, MD, Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02733250
- Sponsor's protocol ID
- CE15.274
- Acronym
- URCOH-PMS-001
- Status last verified
- Jun 2018
- First submitted
- 15 Mar 2016
- Last updated
- 16 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. doi: 10.1200/JCO.2011.39.5848. Epub 2012 Apr 30.
PubMed 22547591
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Pembrolizumab in Combination With Nab-Paclitaxel in Patients With Unresectable Stage III or Stage IV Non-Small Cell Lung Carcinoma
- ClinicalTrials.gov ID
- NCT02733250
- Acronym / sponsor ID
- URCOH-PMS-001 / CE15.274
- Conditions
- Lung Cancer
- Keywords
- NSCLC, Pembrolizumab, Nab-paclitaxel
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Collaborators
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Merck Canada Inc., Celgene, Jewish General Hospital
- Study start
- 13 Mar 2017 (actual)
- Primary completion
- 13 Apr 2019 (actual)
- Study completion
- 13 Dec 2019 (actual)
- First posted
- 11 Apr 2016 (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.
The purpose of this study is to determine the optimal dose of nab-paclitaxel to be safely administered in combination with pembrolizumab in patients with advanced inoperable non-small cell lung cancer. The study is also aimed at evaluating the efficacy of the combination therapy.
Detailed description
This is a phase 1/2, open-label, proof of concept study of nab-paclitaxel administered in combination with pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC).
Part 1 of the study will assess the dose limiting toxicity (DLT) of nab-paclitaxel in combination with a fixed dose of pembrolizumab (200 mg administered on day 1 of each 21 day cycle). Dose escalation for nab-paclitaxel will be conducted according to the "3+3 design" until the recommended phase 2 dose (RP2D) is determined.
Part 2 of the study will evaluate the administration of pembrolizumab at a dose of 200 mg every 3 weeks in combination with nab-paclitaxel at the RP2D. Determining the RP2D will classify the treatment combination as safe and allow for an expansion of the study population, which will ultimately lead to further assessments of safety and tolerability as well as an evaluation of the anti-tumoral effect of the proposed treatment combination.
Using Simon's optimal 2-stage design for Phase II clinical trials, we determined that a sample size of 36 patients would be adequate to test the proposed hypothesis.
The primary efficacy analysis of overall response rate (ORR) will be interpreted as follows: 1) if less than 9 partial response (PR) or complete response (CR) are recorded, the combination of nab-paclitaxel and pembrolizumab provides less than additive effects and is not likely to be clinically superior compared to pembrolizumab alone based on an ORR assessment; 2) however, if 9 or more PR or CR are recorded, the treatment combination warrants further clinical study. This could take the form of an extended phase II (to reach the 97 patients calculated from the model) or a phase III study.
Treatment will continue until disease progression (as per RECIST 1.1), unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, investigator's noncompliance with trial treatment or procedures requirements, the subject receives 24 months of uninterrupted treatment or 35 administrations of study medication (whichever is later), or administrative reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Nab-Paclitaxel | Other | Biological: Pembrolizumab, Drug: Nab-PaclitaxelPhase I will determine the recommended Phase II dose (RP2D) of nab-paclitaxel when given in combination with pembrolizumab. Escalation for nab-paclitaxel will be conducted following a "3+3" design. First cohort of 3 patients will receive nab-paclitaxel on Days 1 and 8 at a dose of 100 mg/m2 intravenous (IV) in combination with pembrolizumab at 200 mg IV every 3 weeks. If no dose limiting toxicities (DLT) occur, the dose of nab-paclitaxel will be escalated to 100 mg/m2 on Days 1, 8 and 15 every 3 weeks. The dose of pembrolizumab will remain the same. If no DLTs occur, dose level 2 will be defined as the RP2D. In the Phase II, pembrolizumab will be administered at 200 mg IV every 3 weeks and nab-paclitaxel will be administered at the RP2D. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Be willing and able to provide written informed consent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Have unresectable stage III (not eligible to curative-intent chemo-radiotherapy) or stage IV non-small cell lung cancer (NSCLC) according to the Clarification of Malignant Tumours (TNM) staging system for lung cancer (7th edition).
- Patients must be willing to undergo a biopsy procedure before the start of treatment unless these two conditions are met: 1) the biopsy must have been conducted after progression or intolerance to systemic first-line treatment as stated in criteria 7 and; 2) all the planned correlative analyses can be conducted on the available tissue.
- Have measurable/evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Key exclusion criteria (13 listed)
- Has a known epidermal growth factor receptor (EGFR) sensitizing (activating) mutation and/or anaplastic lymphoma kinase (ALK) translocation.
- Has an unknown EGFR and ALK status.
- Has received prior therapy with paclitaxel or docetaxel for NSCLC.
- Has received systemic steroid therapy within three days prior to the first dose of study treatment or receiving any other form of systemic immunosuppressive medication.
- Has a history of allogeneic tissue/solid 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 |
|---|---|---|
| PembrolizumabAlso: Keytruda200mg IV Day 1 of each 21 cycles | Biological | Pembrolizumab + Nab-Paclitaxel |
| Nab-PaclitaxelAlso: Abraxane100mg/m2 IV Day 1, 8 and 15 of every 21 day cycles | Drug | Pembrolizumab + Nab-Paclitaxel |
Primary outcome
Safety and tolerability of nab-paclitaxel in combination with pembrolizumab as measured by incidence of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities.
Time frame: Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose.
Safety analysis will be based on subjects who experienced toxicities as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Safety will be assessed by quantifying the toxicities and grades experienced by subjects who received at least one dose of pembrolizumab and nab-paclitaxel, including serious adverse events (SAEs) and event of clinical interest (ECIs).
Objective Response Rate (ORR)
Time frame: up to 56 months
Defined as the proportion of patients with best overall response or either complete response or partial response, which will be recorded based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or the Immune related response criteria (irRC).
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 16 Feb 2021.
- Background: PubMed 22547591Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. doi: 10.1200/JCO.2011.39.5848. Epub 2012 Apr 30.
- Individual participant dataSharing planned: Undecided
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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.
Normand Blais, MD principal investigator
Centre hospitalier de l'Université de Montréal (CHUM)
2 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 Pembrolizumab and Nab-Paclitaxel in people with Lung Cancer, run by Centre hospitalier de l'Université de Montréal (CHUM) at 2 sites in Canada.
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 6 inclusion and 13 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 16 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
Safety and tolerability of nab-paclitaxel in combination with pembrolizumab as measured by incidence of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities. (time frame: Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose.). 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?
On the ClinicalTrials.gov record for NCT02733250, which also lists 1 linked publication.
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 16 Feb 2021.