We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase II Trial of Sequential Consolidation With Pembrolizumab Followed by Nab-paclitaxel

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02684461
Recruitment Status : Completed
First Posted : February 18, 2016
Results First Posted : June 3, 2022
Last Update Posted : June 3, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:
The purpose of this research study is to test the effectiveness of three treatment arms that are designed to improve survival in patients with non-small cell lung cancer. Eligible subjects could be randomized to four (4) cycles of chemotherapy followed by immunotherapy, or immunotherapy followed by chemotherapy, or four cycles of chemotherapy plus immunotherapy.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: Pembrolizumab Phase 2

Detailed Description:
This open-label, three-arm, non-comparative randomized phase II study is designed to evaluate three different sequences of double-consolidation with the humanized monoclonal antibody targeted against cell surface receptor programmed cell death-1 (PD-1), pembrolizumab, and nab-paclitaxel in patients with advanced Non small cell lung cancer post induction chemotherapy. While the goal of each arm is to guarantee exposure to each of these two agents to patients who have not progressed post induction chemotherapy, they do so with different sequence. In ARMs A and B, consolidation is sequential, with either pembrolizumab followed by nab-paclitaxel (ARM A), or nab-paclitaxel followed by pembrolizumab (ARM B). In ARM C, consolidation is concurrent, with the two agents administered concurrently. As of July 24, ARMs B and C are closed, and no patients will be enrolled on this study. ARM A remains open to enrollment.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Sequential Consolidation With Pembrolizumab Followed by Nab-paclitaxel After Standard First-Line Induction Chemotherapy in Advanced NSCLC
Actual Study Start Date : September 13, 2016
Actual Primary Completion Date : November 19, 2021
Actual Study Completion Date : November 19, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A: Sequential Consolidation
Completion of four cycles of Sequential Consolidation of Pembrolizumab 200mg every 21 days and then four cycles Nab-paclitaxel 100 mg/mg2 on day 1 and day 8 every 21 days
Drug: Pembrolizumab

Receive Pembrolizumab 200 mg on day 1 every 21 days for four cycles.

Receive nab-paclitaxel 100 mg/m2 on day 1 and day 8 every 21 days for four cycles.

Other Names:
  • Keytruda
  • nab-paclitaxel

Active Comparator: Arm B: Sequential Consolidation
Completion of 4 cycles of Sequential Consolidation of Nab-paclitexel 100 mg/m2 on day 1 and day 8 every 21 days and then Pembrolizumab 200 mg every 21
Drug: Pembrolizumab

Receive Pembrolizumab 200 mg on day 1 every 21 days for four cycles.

Receive nab-paclitaxel 100 mg/m2 on day 1 and day 8 every 21 days for four cycles.

Other Names:
  • Keytruda
  • nab-paclitaxel

Active Comparator: Arm C: Concurrent Consolidation
Concurrent Consolidation of Nab paclitaxel 100 mg/m2 on day 1 and day 8 plus Pembrolizumab 200 m5 on day 1 every 21 days for four cycles
Drug: Pembrolizumab

Receive Pembrolizumab 200 mg on day 1 every 21 days for four cycles.

Receive nab-paclitaxel 100 mg/m2 on day 1 and day 8 every 21 days for four cycles.

Other Names:
  • Keytruda
  • nab-paclitaxel




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 60 months ]
    Overall survival is defined as the time from day 1 of treatment to death from any cause. Median overall survival was calculated for each arm.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to 60 months ]

    PFS is defined as the time from first day of treatment until disease progression as defined by the response evaluation criteria in solid tumors (RECIST 1.1) and and Immune Related Response Criteria (irRC), or death from any cause death or progression.

    RECIST 1.1 Progressive Disease (PD): >= 20% increase in the sum of the LD of the target lesions, Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, Nonprogressive disease (NPD): No measurable disease at the entrance of the study or otherwise non measurable disease will be assessed for progression.

    irRC Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir; for no new non-target or (irNN) and where irPR or irPD are confirmed by a repeat, consecutive assessment no less than 4 weeks later.


  2. Overall Rates of Response (ORR) [ Time Frame: 6 months ]

    ORR is defined as the number of subjects with complete response + partial response based on RECIST 1.1 and irRC criteria.

    RECIST 1.1 Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >=30% decrease in the sum of the longest diameter (LD) of target lesions.

    irRC Complete Response (irCR): Disappearance of all lesions, no new lesions, lymph nodes < 10 mm in short axis, Partial Response (irPR): ≥30% decrease in the sum of target lesions and non-target lesions are irNN.


  3. Rates of Response in Arm A and Arm B [ Time Frame: 6 months ]
    Rates of Response is defined percent tumor size reduction based RECIST1.1 and irRC criteria (the latter if applicable) after each component of therapy in Arm A and Arm B.

  4. Toxicity Profile [ Time Frame: 6 months ]

    The toxicity profile is classified and defined by both provider and the participants reported outcomes.

    Clinician assessed toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) Participants assessed toxicity will be classified based on the Patient-Reported Outcome version of the CTCAE (PRO-CTCAE).

    Adverse events occurring in greater than two patients or any grade 3 toxicity were included.


  5. Quality of Life (QOL) End of Treatment [ Time Frame: Baseline to End of Treatment (up to 210 Days) ]

    Changes in QOL score for each subject are defined as the difference between the baseline, and at end of treatment.

    QOL will be evaluated using The Functional Assessment of Cancer Therapy-Lung (FACT-Lung) scale at baseline and the end of treatment. The FACT-L is the FACT-G and a lung cancer-specific (LCS) subscale given at baseline and end of treatment. The FACT-G is a 27-item measure of general QOL assessing function in 4 domains: physical well-being, social-family well-being, emotional well-being, and functional well-being. Items are rated by patients on a Likert scale from 0 to 4. Higher scores represent better QOL.


  6. Quality of Life (QOL) 7 Weeks [ Time Frame: Baseline to 7 weeks (40-50 Days) ]

    Changes in QOL score for each subject are defined as the difference between the baseline, and at 7 weeks.

    QOL will be evaluated using The Functional Assessment of Cancer Therapy-Lung (FACT-Lung) scale at baseline and 7 weeks. The FACT-L is the FACT-G and a lung cancer-specific (LCS) subscale given at baseline and at end of treatment. The FACT-G is a 27-item measure of general QOL assessing function in 4 domains: physical well-being, social-family well-being, emotional well-being, and functional well-being. Items are rated by patients on a Likert scale from 0 to 4. Higher scores represent better QOL.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be willing and able to provide written informed consent for this trial
  • Be greater than or equal to 18 years of age on day of signing consent
  • Eastern Cooperative Oncology Group Performance Status less than or equal to 1
  • Histologically or cytologically confirmed confirmed stage IV (metastatic) non small cell lung cancer as defined by American Joint Committee on Cancer (AJCC). Recurrent but not metastatic disease is allowed if deemed incurable.
  • Has completed or scheduled to begin 4-6 cycles of platinum based induction chemotherapy that does not include a taxane
  • Induction may contain, but is not require to contain bevacizumab or cetuximab.
  • Induction with a platinum doublet plus another biologic agent will be allowed following review by the University of North Carolina principal investigator that thee is no additional risk to the subject

NOTE: Evaluable disease is not required for study entry (patients with complete response or response sufficient to preclude measurable lesions are not excluded; such patients will be evaluated for progression free survival and overall survival, but not response)

  • Demonstrate adequate organ function (defined in protocol). All screening labs should be performed within 14 days of treatment initiation.
  • Recovered from all reversible toxicities related to their previous treatment (other than alopecia) less than or equal to grade 1 or baseline; exceptions to this criteria may be allowed at the discretion of the overall principal investigator for toxicities that are not expected to be exacerbated by pembrolizumab or nab paclitaxel
  • Patients with brain metastases may participate if they have undergone appropriate treatment for the lesion)s), are at least two weeks post treatment without evidence for post-treatment progression, have no significant neurologic symptoms, and no longer require steroids for the reason of brain metastases
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for greater than 1 year. The two birth control methods can be two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from study Visit 1 throughout the study period up to 120 days after the last dose of study therapy.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  • Patients with epidermal growth factor receptor (EGFR) mutations expected to be sensitive to epidermal growth factor receptor (EGFR) inhibitors and patients with Echinoderm Microtubule-Associated Protein like 4 anaplastic lymphoma kinase (EML4/ALK) translocations are excluded, unless all available FDA approved targeted therapy options have been utilized. NOTE: In contrast to the above a patient with an EGFR mutation who has been treated with a first-generation and third generation TKIs and then with four cycles of carboplatin plus pemetrexed would be eligible
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1. Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier. Exceptions to these criteria may be allowed at the discretion overall principal for toxicities that are not expected to be exacerbated by pembrolizumab or nab-paclitaxel
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Has inadequate home environment or social support to safely complete the trial procedures
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-programmed cell death-1 (PD-1) , anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • Known hypersensitivity to protein bound paclitaxel
  • Has received prior therapy with any taxane chemotherapy
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  • Has known active Hepatitis B or Hepatitis C
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment
  • Has a history of non-infectious pneumonitis that required steroids or evidence of interstitial lung disease or current active, non-infectious pneumonitis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02684461


Locations
Layout table for location information
United States, North Carolina
UNC Lineberger Comprehsive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Rex Cancer Center
Raleigh, North Carolina, United States, 27607
Rex Cancer Center of Wakefield
Raleigh, North Carolina, United States, 27614
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Virginia
Inova Schar Cancer Institute
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Merck Sharp & Dohme LLC
Investigators
Layout table for investigator information
Principal Investigator: Jared Weiss, MD University of North Carolina, Chapel Hill
  Study Documents (Full-Text)

Documents provided by UNC Lineberger Comprehensive Cancer Center:
Additional Information:
Layout table for additonal information
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02684461    
Other Study ID Numbers: LCCC 1516
First Posted: February 18, 2016    Key Record Dates
Results First Posted: June 3, 2022
Last Update Posted: June 3, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
lung cancer
PD-1 antibody
immune checkpoint blockade
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Pembrolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological