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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01833143
First received: April 11, 2013
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Non-Small Cell Lung Cancer
Drug: Bortezomib
Drug: Acyclovir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • efficacy of single-agent subcutaneous bortezomib [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The following evaluations will be conducted to assess the efficacy of bortezomib - radiographic response rate by RECIST v1.1


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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,).


Estimated Enrollment: 25
Study Start Date: April 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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
  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: NCT01833143

Contacts
Contact: Gregory Riely, MD PhD 646-888-4199
Contact: Paul Paik, MD 646-888-4202

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Gregory Riely, MD, PhD    646-888-4202      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Gregory Riely, MD, PhD    646-888-4202      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Gregory J Riely, MD         
Contact: Paul Paik, MD    646-888-4202      
Principal Investigator: Gregory J Riely, MD         
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Gregory Riely, MD, PhD    646-888-4202      
Memoral Sloan Kettering Cancer Center at Phelps Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Gregory Riely, MD, PhD    646-888-4202      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Gregory Riely, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01833143     History of Changes
Other Study ID Numbers: 12-222
Study First Received: April 11, 2013
Last Updated: February 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
KRAS-Mutant
Bortezomib
KRAS G12D
12-222

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Acyclovir
Bortezomib
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014