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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT02120807
First received: April 21, 2014
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Stage IV Lung Adenocarcinoma
Drug: Certolizumab
Drug: cisplatin
Drug: pemetrexed
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Certolizumab in Combination With Chemotherapy for Patients With Stage IV Lung Adenocarcinomas

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated does (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • Immunohistochemical staining [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 34
Study Start Date: April 2014
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: certolizumab, cisplatin and pemetrexed
All patients will receive certolizumab with 6 cycles of cisplatin and pemetrexed. Each cycle of chemotherapy will be 3 weeks. Certolizumab will be administered 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, and 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 and 400mg. 200mg was selected for dose level 1 since it is 50% of the dose FDA-approved for certolizumab in the treatment of rheumatoid arthritis and inflammatory bowel disease.
Drug: Certolizumab Drug: cisplatin Drug: pemetrexed

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02120807

Contacts
Contact: Paul Paik, MD 646-888-4202
Contact: Mark Kris, MD 646-888-4197

Locations
United States, New Jersey
Memorial Sloan Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Paul Paik, MD    646-888-4202      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Paul Paik, MD    646-888-4202      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Paul Paik, MD    646-888-4202      
Contact: Mark Kris, MD    646-888-4197      
Principal Investigator: Paul Paik, MD         
Memorial Sloan Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Paul Paik, MD    646-888-4202      
Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Paul Paik, MD    646-888-4202      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Paul Paik Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02120807     History of Changes
Other Study ID Numbers: 13-063
Study First Received: April 21, 2014
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Certolizumab
Cisplatin
Pemetrexed
thoracic
13-063

Additional relevant MeSH terms:
Adenocarcinoma
Lung Neoplasms
Carcinoma
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Certolizumab pegol
Cisplatin
Immunoglobulin Fab Fragments
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014