Lung Cancer
Conditions
Brief summary
ABRAXANE, based on results from prior studies, is a promising drug in squamous cell carcinoma of the lung. This study will help to explore the combination of ABRAXANE and carboplatin more thoroughly in the subgroup of patients who had the best response in prior studies as well as determine whether there are any biomarkers which can predict for response.
Detailed description
This is a single arm phase II study for subjects receiving first line therapy for metastatic squamous cell lung cancer. Following informed consent and eligibility check, all subjects will receive therapy with carboplatin and ABRAXANE on an outpatient basis. A total of 50 subjects will be enrolled over an enrollment period of about 24 months. Interim analyses will be conducted after the enrollment of subject 15, subject 30, and subject 45. Tissue biomarkers will be analyzed at baseline; and blood biomarkers will be analyzed at baseline, pre-dose on cycles 3 and 5, and then within 30 days of last dose of study treatment.
Interventions
DRUGCarboplatin
Dosing: AUC = 6; on Day 1
DRUGAbraxane
100 mg/m\^2; Days 1, 8, 15
Sponsors
Celgene
Wake Forest University Health Sciences
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
* Histologically confirmed stage IV non-small cell lung cancer with predominantly squamous histology * No prior systemic treatment for metastatic disease. Patients who have received prior adjuvant chemotherapy for early-stage lung cancer are eligible if at least 12 months have elapsed between the date of final chemotherapy administration and the date of consent * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with CT scan, MRI, or calipers by clinical exam * Biopsy accessible disease * Patients with previous radiotherapy as definitive therapy for locally advanced non-small cell lung cancer are eligible, as long as the recurrence is outside the original radiation therapy port. Definitive radiation therapy must have been completed \>4 weeks prior to the date the informed consent is signed * Age \>18 years * ECOG performance status less than or equal to 1 * If patient has brain metastasis, the disease must be stable (treated and/or asymptomatic) for at least 4 weeks prior to first dose of study treatment * Bilirubin \< 1.5 mg/dL * Adequate liver function: AST and ALT \<= 2.5x upper limit of normal, alkaline phosphatase \<= 2.5x upper limit of normal, unless bone metastasis is present (\< 5x upper limit of normal) in the absence of liver metastasis * Adequate bone marrow function: Platelets \>100,000 cells/mm3, Hemoglobin \> 9.0g/dL and ANC \> 1,500 cells/mm3 * Adequate renal function with creatinine \<1.5 mg/dL is recommended * Females of childbearing potential and sexually active males must use an effective contraception method during treatment and for six months after completing treatment * Negative serum or urine B-hCG pregnancy test at screening for patients of childbearing potential * Patients must have \< Grade 2 pre-existing peripheral neuropathy (per CTCAE version 4.0) * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Received prior systemic therapy for metastatic disease * Received limited field radiation for palliation \<= 2 weeks prior to starting study treatment and/or from whom \>= 30% bone marrow was irradiated * Receiving any other investigational agents * Known hypersensitivity to either carboplatin or ABRAXANE * Uncontrolled and current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or breast feeding * Other active malignancies * Neuropathy greater than or equal to grade 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Response | Up to a planned 18 weeks | The primary endpoint is a binary variable determined for each patient indicating whether or not they achieved a complete response (CR) or a partial response (PR) as per RECIST 1.1 (where a CR is indicated by disappearance of all target and non target lesions and a PR is indicated by \>= 30% decrease in sum of longest diameter of target lesions with baseline as reference). Because overall response is the primary endpoint for this study, best responses of CR or PR must be confirmed by a subsequent radiologic assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Stable Disease or Response | 18 weeks | Disease control is calculated for each subject indicating whether or not they achieved an overall response of stable disease or better by RECIST 1.1 (where a CR is indicated by disappearance of all target and non target lesions, a PR is indicated by \>= 30% decrease in sum of longest diameter of target lesions with baseline as reference, and SD is neither sufficient shrinkage to qualify for PR nor sufficient growth, \>=20%, to indicate progression). |
| Progression Free Survival | From date of treatment start to date of progression/death, or censored as described above; assessed for approximately 3 years | PFS is defined as time from enrollment to time of progression or death. Disease progression (PD) may be determined objectively per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, where PD is defined as a 20% increase in the sum of longest diameters of target lesions, a measurable increase in non-target lesion, or appearance of new lesions) or subjectively as determined by investigator (with evidence documented in the medical records). If the subject died without documented PD, date of progression will be date of death. For surviving subjects who did not have documented PD, PFS was censored at last radiologic assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS was censored at last radiologic assessment prior to commencement of subsequent therapy. Subjects who experienced a PFS event following an interval equal to two or more scheduled radiologic assessments were censored at last assessment prior to first missed assessment. |
| Overall Survival | From date of treatment start to date of death, or censored as described above; assessed for approximately 3 years | OS is defined as the duration of time from enrollment to the date of death from any cause. Subjects who were alive or lost to follow-up at the time of the analysis were censored at the last known date they were alive. |
| Duration of Response | From date of response to date of progression/death, or censored as described above; assessed for approximately 3 years. | For subjects who achieve a CR or PR, response duration will be measured from the first day of the response until the day on which progressive disease (PD) or death occurred. The censoring method will be the same as that described for PFS. |
| Duration of Disease Control | From date of treatment start to date of progression, or censored as described above; assessed for approximately 3 years | For subjects who achieve SD or better, duration of disease control will be measured from the treatment start date until the day on which progressive disease (PD) or death occurred. The censoring method will be the same as that described for PFS. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin + Abraxane Carboplatin (AUC = 6; on Day 1) plus Abraxane (nab-paclitaxel; 100 mg/m\^2; Days 1, 8, 15) for 6 21-day cycles. Treatment was discontinued if: disease progression, unacceptable toxicity, withdrawn consent, or completion of treatment | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
| Overall Study | Still On Study in Follow-Up | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Carboplatin + Abraxane |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 66.09 years STANDARD_DEVIATION 8.95 |
| ECOG at Baseline ECOG 0 | 5 Participants |
| ECOG at Baseline ECOG 1 | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Primary Tumor Site - Lung | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 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 | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 9 Participants |
| Smoking Status Current Smoker | 4 Participants |
| Smoking Status Previous Smoker | 7 Participants |
| Stage - IV | 11 Participants |
| Tumor Grade High | 7 Participants |
| Tumor Grade Low | 4 Participants |
| Tumor Histology - Squamous NSCLC | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 2 / 11 |
Outcome results
Primary
Number of Participants With a Response
The primary endpoint is a binary variable determined for each patient indicating whether or not they achieved a complete response (CR) or a partial response (PR) as per RECIST 1.1 (where a CR is indicated by disappearance of all target and non target lesions and a PR is indicated by \>= 30% decrease in sum of longest diameter of target lesions with baseline as reference). Because overall response is the primary endpoint for this study, best responses of CR or PR must be confirmed by a subsequent radiologic assessment.
Time frame: Up to a planned 18 weeks
Population: The efficacy population (or evaluable population) is defined as all subjects who have measurable disease present at baseline, have received at least one dose of study therapy, and have had their disease re-evaluated (either clinically or radiographically)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carboplatin + Abraxane | Number of Participants With a Response | 4 Participants |
p-value: 0.16195% CI: [0.109, 0.692]Fisher Exact
Secondary
Duration of Disease Control
For subjects who achieve SD or better, duration of disease control will be measured from the treatment start date until the day on which progressive disease (PD) or death occurred. The censoring method will be the same as that described for PFS.
Time frame: From date of treatment start to date of progression, or censored as described above; assessed for approximately 3 years
Population: Efficacy analyses were conducted on the population of subjects who began Carboplatin + Abraxane treatment. Duration of disease control was conducted specifically on those subjects in the efficacy population who achieved disease control (stable disease or better).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin + Abraxane | Duration of Disease Control | 7.3 months |
95% CI: [3, 13]
Secondary
Duration of Response
For subjects who achieve a CR or PR, response duration will be measured from the first day of the response until the day on which progressive disease (PD) or death occurred. The censoring method will be the same as that described for PFS.
Time frame: From date of response to date of progression/death, or censored as described above; assessed for approximately 3 years.
Population: Efficacy analyses were conducted on the population of subjects who began Carboplatin + Abraxane treatment. Duration of response was conducted specifically on those subjects in the efficacy population who achieved objective response (PR or CR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin + Abraxane | Duration of Response | 10.8 months |
95% CI: [4.9, 11.9]
Secondary
Number of Subjects With Stable Disease or Response
Disease control is calculated for each subject indicating whether or not they achieved an overall response of stable disease or better by RECIST 1.1 (where a CR is indicated by disappearance of all target and non target lesions, a PR is indicated by \>= 30% decrease in sum of longest diameter of target lesions with baseline as reference, and SD is neither sufficient shrinkage to qualify for PR nor sufficient growth, \>=20%, to indicate progression).
Time frame: 18 weeks
Population: The efficacy population (or evaluable population) is defined as all subjects who have measurable disease present at baseline, have received at least one dose of study therapy, and have had their disease re-evaluated (either clinically or radiographically).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carboplatin + Abraxane | Number of Subjects With Stable Disease or Response | 9 Participants |
95% CI: [0.482, 0.977]
Secondary
Overall Survival
OS is defined as the duration of time from enrollment to the date of death from any cause. Subjects who were alive or lost to follow-up at the time of the analysis were censored at the last known date they were alive.
Time frame: From date of treatment start to date of death, or censored as described above; assessed for approximately 3 years
Population: Efficacy analyses were conducted on the population of subjects who began Carboplatin + Abraxane treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin + Abraxane | Overall Survival | 30 months |
Secondary
Progression Free Survival
PFS is defined as time from enrollment to time of progression or death. Disease progression (PD) may be determined objectively per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, where PD is defined as a 20% increase in the sum of longest diameters of target lesions, a measurable increase in non-target lesion, or appearance of new lesions) or subjectively as determined by investigator (with evidence documented in the medical records). If the subject died without documented PD, date of progression will be date of death. For surviving subjects who did not have documented PD, PFS was censored at last radiologic assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS was censored at last radiologic assessment prior to commencement of subsequent therapy. Subjects who experienced a PFS event following an interval equal to two or more scheduled radiologic assessments were censored at last assessment prior to first missed assessment.
Time frame: From date of treatment start to date of progression/death, or censored as described above; assessed for approximately 3 years
Population: Efficacy analyses were conducted on the population of subjects who began Carboplatin + Abraxane treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin + Abraxane | Progression Free Survival | 7.3 months |
95% CI: [2.2, 13]