Certolizumab, Cisplatin, and Pemetrexed Disodium in Treating Patients with Previously Untreated Stage IV Lung Cancer

Status: Active

Description

This phase I clinical trial studies the side effects and the best dose of certolizumab when given together with cisplatin and pemetrexed disodium in treating patients with previously untreated lung cancer that has spread to other places in the body. Certolizumab reduces inflammation and may make chemotherapy more effective. It may also prevent tumor cells from spreading to new organs. Drugs used in chemotherapy, such as cisplatin and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving certolizumab together with cisplatin and pemetrexed disodium may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Previously untreated stage IV lung adenocarcinoma confirmed at the Memorial Sloan-Kettering Cancer Center (MSKCC)
  • Karnofsky performance status >= 70
  • Patients with locally treated, stable, and/or asymptomatic brain metastases are eligible
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Hemoglobin >= 8 g/dL
  • Platelets >= 100 x 10^9/L
  • Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert's syndrome)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (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 >= 60 ml/min for patients with creatinine levels above institutional normal
  • Negative purified protein derivative (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 1.1
  • 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 cytology or bone specimen * Biopsy site must be amenable to re-biopsy at the end of study ** In the event that the tumor resolves on treatment, another site amenable to biopsy will be selected
  • 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 (Common Terminology Criteria for Adverse Events [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 * 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 human immunodeficiency virus (HIV) infection requiring antiretroviral medications and those with acquired immunodeficiency syndrome (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

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Paul K. Paik
Phone: 646-888-4202

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Paul K. Paik
Phone: 646-888-4202
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Paul K. Paik
Phone: 646-888-4202
Sleepy Hollow
Memorial Sloan Kettering Sleepy Hollow
Status: Active
Contact: Paul K. Paik
Phone: 646-888-4202
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Paul K. Paik
Phone: 646-888-4202
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Paul K. Paik
Phone: 646-888-4202

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) of the combination of certolizumab plus cisplatin and pemetrexed (pemetrexed disodium) in patients with untreated stage IV lung adenocarcinoma.

SECONDARY OBJECTIVES:

I. Objective response rate.

II. Progression-free survival (PFS).

CORRELATIVE OBJECTIVES:

I. To evaluate the on-target effect of certolizumab pegol on the tumor necrosis factor (TNF)-alpha/chemokine (C-X-C motif) ligand 1-2 (CXCL1-2)/S00A8/9 axis through serial quantification of serum TNF-alpha, CXCL1-2, and S100A8/9 concentrations.

II. To evaluate the on-target effect of certolizumab pegol on the TNF-alpha/CXCL1-2/S00A8/9 axis through immunohistochemical staining of these factors and related pathways using pre- and post-treatment biopsy specimens.

OUTLINE: This is a dose-escalation study of certolizumab.

Patients receive certolizumab subcutaneously (SC) on day 1 of weeks 1, 3, 5, 9, 13, and 17, and cisplatin intravenously (IV) and pemetrexed disodium IV on day 1 of weeks 1, 4, 7, 10, 13, and 16 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Paul K. Paik

Trial IDs

Primary ID 13-063
Secondary IDs NCI-2014-01021
Clinicaltrials.gov ID NCT02120807