Pembrolizumab With Nab-Paclitaxel in Non-Small Cell Lung Cancer (URCOH-PMS-001)

February 12, 2021 updated by: Centre hospitalier de l'Université de Montréal (CHUM)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
      • Montreal, Quebec, Canada, H2X 3E4
        • Centre Hospitalier de l'Universite de Montreal (CHUM)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Pembrolizumab + Nab-Paclitaxel
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.
Biological: Pembrolizumab
200mg IV Day 1 of each 21 cycles
Other Names:
  • Keytruda
Drug: Nab-Paclitaxel
100mg/m2 IV Day 1, 8 and 15 of every 21 day cycles
Other Names:
  • Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose.
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).
up to 56 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborators

Celgene
Jewish General Hospital
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Merck Canada Inc.

Investigators

  • Principal Investigator: Normand Blais, MD, Centre Hospitalier de l'Universite de Montreal (CHUM)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 13, 2017

Primary Completion (ACTUAL)

April 13, 2019

Study Completion (ACTUAL)

December 13, 2019

Study Registration Dates

First Submitted

March 15, 2016

First Submitted That Met QC Criteria

April 8, 2016

First Posted (ESTIMATE)

April 11, 2016

Study Record Updates

Last Update Posted (ACTUAL)

February 16, 2021

Last Update Submitted That Met QC Criteria

February 12, 2021

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CE15.274

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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