Working... Menu

Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D

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. Identifier: NCT01833143
Recruitment Status : Active, not recruiting
First Posted : April 16, 2013
Last Update Posted : May 3, 2019
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to test the drug Bortezomib to see how well it works. The investigators want to find out what effects, good or bad, it has on patients with a limited smoking history or who have a specific mutation associated with their lung cancer.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Bortezomib Drug: Acyclovir Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D
Study Start Date : April 2013
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Bortezomib
Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 2 weeks, or at the discretion of the treating physician or patient.
Drug: Bortezomib
Drug: Acyclovir

Primary Outcome Measures :
  1. efficacy of single-agent subcutaneous bortezomib [ Time Frame: 2 years ]
    The following evaluations will be conducted to assess the efficacy of bortezomib - radiographic response rate by RECIST v1.1

Secondary Outcome Measures :
  1. Efficacy [ Time Frame: 2 years ]
    Secondary endpoints of progression free survival, 8-week stable disease, and overall survival will be evaluated according to RECIST v.1.1 criteria as well.

  2. Toxicity [ Time Frame: 2 years ]
    Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE v4.0,).

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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Pathologic or cytologic evidence of non-small cell lung cancer (NSCLC)
  • Documented KRAS mutation
  • History of smoking < 100 cigarettes (never-smoker) OR patient with a KRAS G12D mutation regardless of smoking history
  • Clinical stage IIIB/IV or recurrent/medically inoperable NSCLC
  • Age ≥ 18 years
  • Three (3) weeks since last chemotherapy, and three (3) weeks since prior radiation therapy and recovered from treatment
  • Karnofsky performance status ≥ 70%
  • Adequate hematologic, and/or hepatic function WBC ≥ 3,000/ul or absolute neutrophil count ≥ 1,000/ul Hemoglobin ≥ 9.0 g/dl Platelet count ≥ 100,000/ul AST ≤ 2.0 X ULN (upper limit of normal)
  • Total bilirubin ≤1.5 x ULN Measurable indicator lesions by RECIST v1.1 criteria.
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
  • Male subjects must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.

Exclusion Criteria:

  • Uncontrolled central nervous system metastases defined as any lesion which is either a. symptomatic, or requiring escalating doses of corticosteroids
  • Significant medical history or unstable medical condition such as uncontrolled diabetes myocardial infarction within 6 months prior to enrollment New York Heart Association Class III or IV heart failure severe uncontrolled ventricular arrythmias uncontrolled angina ECG evidence of acute ischemia or active conduction system abnormalities
  • Baseline ≥ grade 2 peripheral neuropathy by CTCAE v 4.0 (Appendix B)
  • Known hypersensitivity to boron or mannitol
  • Female patients who are pregnant/lactating or have a positive serum or urine β-hCG pregnancy test
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • No active concurrent malignancy, with the exception of in-situ malignancy completely resected basal cell carcinoma or squamous cell carcinomas of the skin low-risk prostate cancer after curative therapy
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial

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 identifier (NCT number): NCT01833143

Layout table for location information
United States, New Jersey
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering Cancer Center at Mercy Medical Center
Rockville Centre, New York, United States, 11570
Memoral Sloan Kettering Cancer Center at Phelps
Sleepy Hollow, New York, United States, 10591
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Millennium Pharmaceuticals, Inc.
Layout table for investigator information
Principal Investigator: Gregory Riely, MD, PhD Memorial Sloan Kettering Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT01833143     History of Changes
Other Study ID Numbers: 12-222
First Posted: April 16, 2013    Key Record Dates
Last Update Posted: May 3, 2019
Last Verified: May 2019

Keywords provided by Memorial Sloan Kettering Cancer Center:

Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents