Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Bortezomib; Acyclovir
Intervention MeSH terms: Acyclovir; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: KRAS-Mutant; Bortezomib; KRAS G12D; 12-222

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.
    

Eligibility 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             not part of normal medical care, with the understanding that consent may be withdrawn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