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

NCT01833143 | Completed Phase 2 Results

• 1 other identifier: 12-222
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 5

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

KRAS-Mutant; Bortezomib; KRAS G12D; 12-222

Outcome Measures

Primary Outcomes (1)

• Radiographic Response Rate

  The following evaluations will be conducted to assess the efficacy of bortezomib - radiographic response rate by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  2 years

Secondary Outcomes (3)

• Progression Free Survival

  2 years

• Participants Evaluated for Toxicity

  2 years

• Overall Survival

  2 years

Study Arms (1)

Bortezomib

EXPERIMENTAL

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

Interventions

Bortezomib DRUG

Bortezomib

Acyclovir DRUG

Bortezomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (5)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Memoral Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, 10591, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bortezomib; Acyclovir

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Gregory Riely, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

rielyg@mskcc.org

646-608-3913

Study Officials

• Gregory Riely, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2013
• First Posted: April 16, 2013
• Study Start: April 11, 2013
• Primary Completion: August 28, 2019
• Study Completion: August 28, 2019
• Last Updated: August 4, 2020
• Results First Posted: July 23, 2020

Record last verified: 2019-08

Locations

US (5)