Non-Small Cell Lung Cancer
Conditions
Keywords
KRAS-Mutant, Bortezomib, KRAS G12D, 12-222
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.
Interventions
DRUGBortezomib
DRUGAcyclovir
Sponsors
Millennium Pharmaceuticals, Inc.
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Response Rate | 2 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 2 years | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Participants Evaluated for Toxicity | 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,). |
| Overall Survival | 2 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not Treated | 1 |
Baseline characteristics
| Characteristic | Bortezomib |
|---|---|
| Age, Continuous | 67 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 17 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 17 |
| other Total, other adverse events | 16 / 17 |
| serious Total, serious adverse events | 4 / 17 |
Outcome results
Primary
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
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bortezomib | Radiographic Response Rate | Partial Response | 1 Participants |
| Bortezomib | Radiographic Response Rate | Stable Disease | 6 Participants |
| Bortezomib | Radiographic Response Rate | Progression of Disease | 10 Participants |
Secondary
Overall Survival
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib | Overall Survival | 13 months |
Secondary
Participants Evaluated for Toxicity
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,).
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bortezomib | Participants Evaluated for Toxicity | 17 Participants |
Secondary
Progression Free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib | Progression Free Survival | 1 months |