Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Plasma-Adapted First-Line Pembro In NSCLC

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04166487
Recruitment Status : Recruiting
First Posted : November 18, 2019
Last Update Posted : March 25, 2021
Sponsor:
Collaborator:
Inivata
Information provided by (Responsible Party):
Michael L. Cheng, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE November 13, 2019
First Posted Date  ICMJE November 18, 2019
Last Update Posted Date March 25, 2021
Actual Study Start Date  ICMJE January 13, 2020
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
6-month Progression Free Survival rate [ Time Frame: 6 Months ]
Kaplan-Meier method
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2019)
  • Early Plasma Response [ Time Frame: 42 Days (each cycle is 21 days) ]
    Early plasma response is defined as ≥50% reduction in plasma ctDNA max AF between Cycle 1 Day 1 and Cycle 2 Day 1 for patients with high shed [≥0.5% max AF] at Cycle 1 Day 1, or persistent low shed [<0.5% max AF] for patients with low shed at Cycle 1 Day 1.
  • Progression Free Survival [ Time Frame: he time from registration to the earlier of progression or death due to any cause or 30 Months ]
    Kaplan-Meier method will be used to estimate event-time distributions and medians for time-to-event data
  • Overall Survival [ Time Frame: time from registration to death from any cause, and patients who are thought to be alive at the time of final analysis will be censored at the last date of contact or 30 months ]
    Kaplan-Meier method will be used to estimate event-time distributions and medians for time-to-event data
  • Feasibility-adherence to protocol therapy for 4 cycles [ Time Frame: 84 Days (each cycle is 21 days) ]
    Feasibility is defined as a patient's adherence to protocol therapy for 4 cycles
Original Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
  • Early Plasma Response [ Time Frame: 42 Days ]
    Early plasma response is defined as ≥50% reduction in plasma ctDNA max AF between C1D1 and C2D1 for patients with high shed [≥0.5% max AF] at C1D1, or persistent low shed [<0.5% max AF] for patients with low shed at C1D1
  • Progression Free Survival [ Time Frame: he time from registration to the earlier of progression or death due to any cause or 30 Months ]
    Kaplan-Meier method will be used to estimate event-time distributions and medians for time-to-event data
  • Overall Survival [ Time Frame: time from registration to death from any cause, and patients who are thought to be alive at the time of final analysis will be censored at the last date of contact or 30 months ]
    Kaplan-Meier method will be used to estimate event-time distributions and medians for time-to-event data
  • Feasibility-adherence to protocol therapy for 4 cycles [ Time Frame: 84 Days ]
    Feasibility is defined as a patient's adherence to protocol therapy for 4 cycles
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Plasma-Adapted First-Line Pembro In NSCLC
Official Title  ICMJE Pilot Study of Serial Plasma Genotyping to Guide the Adaptive Treatment of Advanced NSCLC Receiving First-line Pembrolizumab
Brief Summary

This research study is studying to see if a blood test, collected at different times during the treatment of metastatic non-small lung cancer, can be used to detect early response in patients being treated with pembrolizumab and use that information to determine whether patients should continue treatment with pembrolizumab or switch treatment to pembrolizumab in combination with chemotherapy.

The names of the study drugs involved in this study are:

  • Pembrolizumab
  • Platinum doublet chemotherapy, which may include the following:

    • Carboplatin and pemetrexed
    • Carboplatin and paclitaxel

The name of the blood test:

- InVision (Inivata, Ltd.)

Detailed Description

This is an open label, single institution, prospective pilot study.

The purpose of this research study is to determine if a blood test, collected at different times during treatment, can be used to detect early response in patients being treated with pembrolizumab for lung cancer and use that information to determine whether patients should continue treatment with pembrolizumab or switch treatment to pembrolizumab in combination with chemotherapy.

-The research study procedures include screening for eligibility and study treatment including evaluations approximately every 3 weeks.

The names of the study drugs involved in this study are:

  • Pembrolizumab
  • Platinum doublet chemotherapy, which may include the following:

    • Carboplatin and pemetrexed
    • Carboplatin and paclitaxel

The name of the blood test:

  • InVision- Inivata

    • This blood test that will help study how participants respond to the study treatment. ---
    • Blood will be collected for this test at a few time points, both before and after participants receive treatment on study.
  • Participants will be on the research study for up to 12 months.
  • It is expected that about 40 people will take part in this research study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • NSCLC Stage IV
  • Metastatic Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Pembrolizumab
    predetermined dose, once per cycle via IV will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle.
    Other Name: Keytruda®
  • Drug: PEMETREXED
    administered per standard practice, once per cycle via IV will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle.
    Other Name: Alimta®
  • Drug: CARBOPLATIN
    administered per standard practice once per cycle via IV will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle.
    Other Name: Paraplatin ®
  • Drug: PACLITAXEL
    administered per standard practice once per cycle via IV will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle.
    Other Names:
    • Taxol®,
    • Onxal
  • Diagnostic Test: InVision
    Plasma draw for clinical test performed at C1D1 and C2D1; plasma draw for research testing performed at other timepoints per protocol.
Study Arms  ICMJE
  • Experimental: Pembrolizumab Cycles 1-2
    • For the first two cycles, Pembrolizumab will be administered at a predetermined dose every 3 weeks.
    • InVision plasma draw will take place at Cycle 1 Day 1 and Cycle 2 Day 1, with return of results to the treating oncologist prior to Cycle 3 Day 1.
    • At Cycle 3, patients will be re-registered per the inclusion criteria into 3 arms;

      • PEMBROLIZUMAB Alone
      • PEMBROLIZUMAB + Doublet Chemotherapy
    Interventions:
    • Drug: Pembrolizumab
    • Diagnostic Test: InVision
  • Experimental: Pembrolizumab Alone, Cycle 3+

    - Following imaging assessment at Cycle 3, participants will continue pembrolizumab alone if the following responses are observed:

    • Response of Partial Response/Complete Response
    • Response of Stable Disease with plasma response
    • Response of Progressive Disease without worsening cancer symptoms AND plasma response
    Intervention: Drug: Pembrolizumab
  • Experimental: Pembrolizumab + Doublet Chemotherapy, Cycles 3+
    • Following imaging assessment at Cycle 3, participants will receive pembrolizumab in combination with platinum doublet chemotherapy if they have a response of stable disease without plasma response, OR no plasma response and response of progressive disease without worsening cancer systems. Platinum doublet should be histology-appropriate and will be given on-label, per treating oncologist.
    • PEMBROLIZUMAB
    • Chemotherapy multiple agents systemic

      • PEMETREXED
      • CARBOPLATIN
      • PACLITAXEL
    Interventions:
    • Drug: Pembrolizumab
    • Drug: PEMETREXED
    • Drug: CARBOPLATIN
    • Drug: PACLITAXEL
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 14, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 1, 2025
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

- Participants must have histologically or cytologically confirmed stage IV NSCLC (AJCC 8th edition).

- Participants must have evaluable disease on imaging per RECIST (measurable disease is not required).

  • No prior treatment with a systemic anti-cancer therapy of any kind for the treatment of stage IV NSCLC. Prior definitive chemoradiation for locally advanced disease, or prior adjuvant or neoadjuvant therapy for early stage disease is permitted if completed ≥6 months prior to initiating study treatment.
  • Age ≥18 years.
  • ECOG performance status 0-2 (see Appendix A)
  • Candidate for combination chemoimmunotherapy per physician assessment.
  • Participants must have normal organ and marrow function as defined below:

    -- absolute neutrophil count ≥1000/mcL

    • platelets ≥100,000/mcL
    • total bilirubin <1.3 mg/dL
    • creatinine <1.6 mg/dL
  • PD-L1 tumor proportion score (TPS) ≥1%, as determined by a CLIA-laboratory.
  • The effects of pembrolizumab on the developing human fetus are unknown. For this reason and because immune checkpoint blockade agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of pembrolizumab administration.

    -- NOTE: a pregnancy test will be required at screening for women of childbearing potential.

  • Ability to understand and the willingness to sign a written informed consent document.
  • Inclusion Criteria for Treatment Continuation at Cycle 3 -- Completion of repeat plasma NGS (InVision) on study, with plasma response defined as ≥50% reduction in plasma ctDNA max AF between C1D1 and C2D1 for patients with high shed [≥0.5% max AF] at C1D1, or continued low shed [<0.5% max AF] for patients with low shed at C1D1.

    • Completion of restaging scans on study, with response determined by central review per RECIST 1.1 criteria
    • For participants continuing pembrolizumab alone:

      • Response of Partial Response or Complete Response at Cycle 3 imaging assessment (as determined by TIMC).

OR --- Response of Stable Disease at Cycle 3 imaging assessment (as determined by TIMC) AND plasma response.

OR

  • Response of Progressive Disease at Cycle 3 imaging assessment (as determined by TIMC) without worsening cancer symptoms (as determined by the treating investigator) AND plasma response.

    -- For participants continuing pembrolizumab + doublet chemotherapy:

  • Response of Stable Disease at Cycle 3 imaging assessment (as determined by TIMC) AND no plasma response.

OR --- Response of Progressive Disease at Cycle 3 imaging assessment (as determined by TIMC) without worsening cancer symptoms (as determined by the treating investigator) AND no plasma response.

- NOTE: Patients with a response of Progressive Disease at Cycle 3 imaging assessment (as determined by TIMC) with worsening cancer symptoms (as determined by the treating investigator) must come off treatment.

Exclusion Criteria:

  • Participants with known sensitizing alterations in EGFR, ALK, ROS1 or BRAF.
  • Participants who have had chemotherapy or radiotherapy within 1 week prior to entering the study.
  • Participants who are receiving any other investigational agents.
  • Participants with uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression. Patients with asymptomatic untreated brain metastases are eligible. Patients with treated CNS disease are eligible if stable disease is clinically confirmed ≥2 weeks after definitive CNS therapy (radiation or surgery), and the patient is not receiving systemic steroids ≥10mg of prednisone equivalent at the time of enrollment.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or other agents used in study.
  • Ongoing or active autoimmune disease requiring systemic steroids of ≥10mg of prednisone equivalent or other systemic immunomodulatory agents at the time of enrollment. Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as psoriasis, vitiligo, and alopecia) not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are allowed.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because pembrolizumab is a Pregnancy Category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding should be discontinued if the mother is treated with pembrolizumab. These potential risks may also apply to other agents used in this study.
  • Participants with a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded from this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael L Cheng, MD michael_cheng@dfci.harvard.edu michael_cheng@dfci.harvard.edu
Contact: Clinical Trials Hotline 877-338-7425
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04166487
Other Study ID Numbers  ICMJE 19-523
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
Responsible Party Michael L. Cheng, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE Inivata
Investigators  ICMJE
Principal Investigator: Michael L Cheng, MD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP