Certolizumab in Combination With Chemotherapy for Patients With Stage IV Lung Adenocarcinomas

January 25, 2023 updated by: Memorial Sloan Kettering Cancer Center

A Phase I Trial of Certolizumab in Combination With Chemotherapy for Patients With Stage IV Lung Adenocarcinomas

The purpose of this study is to test the safety of certolizumab when it is given with the chemotherapy drugs cisplatin and pemetrexed. Cisplatin and pemetrexed are two chemotherapy drugs used in the treatment of lung cancer. The investigators want to find out what effects, good and/or bad, certolizumab has on the patient and lung cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • 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

  • United States
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering at Basking Ridge
    • New York
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Cancer Center @ Suffolk
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering West Harrison
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • Rockville Centre, New York, United States
        • Memorial Sloan Kettering at Mercy Medical Center
      • Sleepy Hollow, New York, United States, 10591
        • Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center

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:

  • Previously untreated stage IV lung adenocarcinoma confirmed at MSKCC
  • Age 18 years or older
  • Karnofsky Performance Status ≥ 70
  • Patients with locally treated, stable, and/or asymptomatic brain metastases are eligible.
  • Adequate bone marrow, liver and renal function, as specified below:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
  • Hemoglobin ≥ 8 g/dL
  • Platelets ≥ 100 x 109/L
  • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert's Syndrome)
  • AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present
  • Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal.
  • Negative PPD test
  • For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment
  • Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter
  • Presence of at least one site of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors
  • Archival tissue (10 Unstained Slides - 5 micron sections) from a core biopsy performed and received within 30 days before signing consent or ability to have a fresh core biopsy performed
  • Biopsy cannot be from any cytology or bone specimen
  • Biopsy site must be amenable to re-biopsy at the end of the study
  • Ability to provide written, informed consent

Exclusion Criteria:

  • Hypersensitivity to platinum agents
  • Ongoing use of investigational agents or use of investigational agents within the last four weeks
  • Prior use of agents for TNF-alpha blockade
  • History of rheumatoid arthritis, inflammatory bowel disease, or psoriatic arthritis
  • Baseline hearing deficit (CTCAE version 4.0 grade 2 or higher)
  • Ongoing bacterial, viral, or antifungal infection requiring antimicrobial treatment with the exception of thrush

  • Active tuberculosis or untreated, latent tuberculosis

    o If a patient has signs, symptoms, or a history suggestive of active tuberculosis, evaluation by an infectious disease physician will be required and active tuberculosis ruled-out prior to enrollment.

  • Acute or chronic Hepatitis B or C infection
  • Known HIV infection requiring antiretroviral medications and those with AIDS
  • Active herpes zoster infection
  • Non-healed infected skin ulcers
  • History of myocardial infarction or unstable angina within the past 12 months
  • Ongoing use of other immunosuppressive medications, including oral steroids and excluding topical steroids
  • Women who are breastfeeding Prior history of other malignancy with the exclusion of localized prostate cancer, non-melanomatous skin cancer, ductal carcinoma or lobular carcinoma in situ of the breast

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: certolizumab, cisplatin and pemetrexed
Patients will receive certolizumab with 6 cycles of cisplatin & pemetrexed. Cycle of chemo will be 3 weeks. Certolizumab will be adm in the following fashion: first dose administered at the time of treatment initiation, second dose will be given after 2 weeks of treatment, third dose after four weeks of treatment, & subsequent doses given every 4 weeks thereafter. Patients will be monitored for progression of disease using RECIST 1.1 with scans to be performed every 6 weeks. Posttreatment biopsies will be performed at the time of treatment discontinuation. Two dose levels of certolizumab will be tested, 200mg & 400mg. A non-therapeutic cohort of 10 patients with adenocarcinomas who will be undergoing standard of care treatment with platinum based chemotherapy + pemetrexed +/- bevacizumab will be consented for blood draws before each cycle of treatment. This blood will be analyzed for cytokines and will serve as a reference for the experimental arm.
Drug: cisplatin
Drug: pemetrexed
Drug: Certolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated does (MTD)
Time Frame: 2 years
A standard 3+3 dose-escalation scheme will be used to test two doses of certolizumab: dose level A (200mg) and dose level B (400mg), in combination with the standard dose of chemotherapy. In addition, two de-escalation doses are planned, if dose level A proves too toxic: dose level C (chemotherapy at 75% of the standard dose + certolizumab 200mg) and dose level D (chemotherapy at 75% of the standard dose + certolizumab 400mg)..The MTD is the highest dose at which ≤ 1/6 patients experiences a DLT. Please see the dose escalation schema for exact dose level details.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 2 years
Patients will be followed from the first drug administration until disease progression (by RECIST 1.1) or death, whichever comes first. Patients alive who have not progressed by the end of the study time will be censored at the time of the last available follow-up. PFS probability will be estimated using Kaplan-Meier methods.
2 years
Immunohistochemical staining
Time Frame: 2 years
Biopsies will be performed pre- and post-treatment in all patients and will undergo immunohistochemical staining of TNF-alpha, CXCL1/2, and S100A8/9. Staining will be scored from 0-4. The difference in IHC score from post-treatment to baseline will be compared between patients who have, at minimum, evidence of stable disease during treatment (CR+PR+SD) and the remaining patients, using non-parametric Wilcoxon signed rank test.
2 years

Collaborators and Investigators

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

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Paul Paik, Memorial Sloan Kettering Cancer Center

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.

Helpful Links

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)

April 15, 2014

Primary Completion (Actual)

January 24, 2023

Study Completion (Actual)

January 24, 2023

Study Registration Dates

First Submitted

April 21, 2014

First Submitted That Met QC Criteria

April 21, 2014

First Posted (Estimate)

April 23, 2014

Study Record Updates

Last Update Posted (Estimate)

January 26, 2023

Last Update Submitted That Met QC Criteria

January 25, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-063

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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