Carcinoma, Non Small Cell Lung
Conditions
Keywords
Carcinoma, non small cell lung, Second line, Third line
Brief summary
The overall purpose of the study is to determine whether or not the inclusion of suramin to standard treatment with docetaxel improves progression-free survival for patients with advanced non-small cell lung cancer in the second and third line settings.
Detailed description
The overall purpose of the study is to determine whether or not the inclusion of suramin to standard treatment with docetaxel improves progression-free survival for patients with advanced non-small cell lung cancer in the second and third line settings. Secondary objectives include: * To compare response rate of patients in both treatment arms * To compare overall survival of patients in both treatment arms * To compare toxicity in both treatment arms * To determine whether the survival benefit from suramin is associated with reduced M-phase entry in peripheral blood lymphocytes
Interventions
DRUGDocetaxel
IV over 60 minutes, 75 mg/m2
DRUGSuramin
IV over 30 minutes
Sponsors
Medical College of Wisconsin
Optimum Therapeutics, LLC
Ohio State University
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically proven diagnosis of non-small cell lung cancer * Documented disease progression after first-line chemotherapy for non-small cell lung cancer * Stable and treated CNS metastasis is allowed * Radiation must be completed at least 2 weeks prior to starting protocol treatment * Major surgery must be completed at least 4 weeks prior to starting protocol treatment * ECOG performance status 0-2 * Sexually active patients must use adequate contraception * Adequate bone marrow function * Adequate renal function * Adequate liver function
Exclusion criteria
* Severe hypersensitivity reaction to docetaxel * Pre-existing grade 3 or 4 neuropathy * Women who are pregnant or breastfeeding * Uncontrolled intercurrent illness * Receipt of 3 or more prior chemotherapy regimens
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival in Months | Up to 1 year | Compare progression-free survival (PFS) in participants with advanced NSCLC treated with docetaxel with or without suramin after failure of first-line chemotherapy. PFS is defined as the duration of time from the time of randomization to time of disease progression or death, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate Per RECIST 1.1 Criteria | Up to 1 year | Response rate per RECIST 1.1, as follows: Complete response (CR): Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis Partial response (PR): At least 30% decrease in the sum of longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters Progressive disease (PD): SLD increased by at least 20% from the smallest value on study (including baseline, if that is smallest). The SLD must also demonstrate an absolute increase of at least 5 mm. (Two lesions increasing from 2mm to 3mm, for example, does not qualify). Stable disease (SD): Neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for PD |
| Overall Survival | Up to 50 months | Compare overall survival of participants in both treatment arms. |
| Number of Participants With Toxicity/Adverse Events From Treatment | Up to 2 years | The investigators will compare the toxicity profiles of the two arms of therapy to determine if the docetaxel + suramin has a more favorable toxicity profile than docetaxel alone. This count includes only adverse events considered definitely, probably, or possibly due to treatment. |
| Evaluation of Peripheral Blood Lymphocytes for DNA Damage-induced Checkpoint Control. | Baseline | The investigators hypothesize that suramin in combination with docetaxel improves response rates and survival by increasing the cancer cell population in the M phase of the cell cycle. The G2-M checkpoint control score, defined as (%M-phase arrested cells after cisplatin+suramin)/(%M-phase arrested cells after cisplatin), is an indicator of the effect of suramin on cell accumulation in the M-phase. G2-M checkpoint control was evaluated as a predictor of PFS and OS in participant receiving suramin by linear correlation. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred from June 2012 through April 2014.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel Docetaxel: IV over 60 minutes, 75 mg/m2
Participants with disease progression on the docetaxel arm were allowed to cross over to the suramin arm. | 40 |
| Docetaxel Plus Suramin Suramin: IV over 30 minutes
Docetaxel: IV over 60 minutes. 56 mg/m2 | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Docetaxel | Docetaxel Plus Suramin | Total |
|---|---|---|---|
| Age, Customized 18-39 years | 0 participants | 0 participants | 0 participants |
| Age, Customized 40-49 years | 1 participants | 2 participants | 3 participants |
| Age, Customized 50-59 years | 18 participants | 11 participants | 29 participants |
| Age, Customized 60-69 years | 17 participants | 16 participants | 33 participants |
| Age, Customized 70-79 years | 3 participants | 9 participants | 12 participants |
| Age, Customized 80-89 years | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American, Not of Hispanic Origin | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White, Not of Hispanic Origin | 38 participants | 35 participants | 73 participants |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 13 Participants | 22 Participants | 35 Participants |
| Sex: Female, Male Male | 27 Participants | 18 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 40 | 37 / 40 |
| other Total, other adverse events | 39 / 40 | 49 / 53 |
| serious Total, serious adverse events | 19 / 40 | 26 / 53 |
Outcome results
Primary
Progression-free Survival in Months
Compare progression-free survival (PFS) in participants with advanced NSCLC treated with docetaxel with or without suramin after failure of first-line chemotherapy. PFS is defined as the duration of time from the time of randomization to time of disease progression or death, whichever occurs first.
Time frame: Up to 1 year
Population: The 13 participants that crossed over to the Docetaxel plus Suramin arm did so after progressing on the standard arm. Their progression-free survival was therefore purely determined by the arm of randomization and not influenced by the cross-over.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Progression-free Survival in Months | 2.8 months |
| Docetaxel Plus Suramin | Progression-free Survival in Months | 1.6 months |
Secondary
Evaluation of Peripheral Blood Lymphocytes for DNA Damage-induced Checkpoint Control.
The investigators hypothesize that suramin in combination with docetaxel improves response rates and survival by increasing the cancer cell population in the M phase of the cell cycle. The G2-M checkpoint control score, defined as (%M-phase arrested cells after cisplatin+suramin)/(%M-phase arrested cells after cisplatin), is an indicator of the effect of suramin on cell accumulation in the M-phase. G2-M checkpoint control was evaluated as a predictor of PFS and OS in participant receiving suramin by linear correlation.
Time frame: Baseline
Population: All participants who yielded good quality PBL samples were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Docetaxel | Evaluation of Peripheral Blood Lymphocytes for DNA Damage-induced Checkpoint Control. | 0.91 G2-M checkpoint control score | Standard Deviation 0.37 |
| Docetaxel Plus Suramin | Evaluation of Peripheral Blood Lymphocytes for DNA Damage-induced Checkpoint Control. | 1.30 G2-M checkpoint control score | Standard Deviation 0.89 |
Secondary
Number of Participants With Toxicity/Adverse Events From Treatment
The investigators will compare the toxicity profiles of the two arms of therapy to determine if the docetaxel + suramin has a more favorable toxicity profile than docetaxel alone. This count includes only adverse events considered definitely, probably, or possibly due to treatment.
Time frame: Up to 2 years
Population: The 13 participants that crossed over did so after progressing on the standard arm. Reported here are the number of participants who experienced adverse events on the arm of randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel | Number of Participants With Toxicity/Adverse Events From Treatment | 35 Participants |
| Docetaxel Plus Suramin | Number of Participants With Toxicity/Adverse Events From Treatment | 31 Participants |
Secondary
Overall Survival
Compare overall survival of participants in both treatment arms.
Time frame: Up to 50 months
Population: The 13 participants that crossed over did so after progressing on the standard arm. The overall survival was determined for the arm of randomization without regard of cross-over. Cross-over was provided as option for participants to have the possible benefit of the new treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Overall Survival | 5.3 months |
| Docetaxel Plus Suramin | Overall Survival | 4.1 months |
Secondary
Response Rate Per RECIST 1.1 Criteria
Response rate per RECIST 1.1, as follows: Complete response (CR): Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis Partial response (PR): At least 30% decrease in the sum of longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters Progressive disease (PD): SLD increased by at least 20% from the smallest value on study (including baseline, if that is smallest). The SLD must also demonstrate an absolute increase of at least 5 mm. (Two lesions increasing from 2mm to 3mm, for example, does not qualify). Stable disease (SD): Neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for PD
Time frame: Up to 1 year
Population: The 13 participants that crossed over to the Docetaxel plus Suramin arm did so after progressing on the standard arm. Their response rate was determined by the arm of randomization and not influenced by the cross-over.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel | Response Rate Per RECIST 1.1 Criteria | Partial Response | 1 participants |
| Docetaxel | Response Rate Per RECIST 1.1 Criteria | Stable Disease | 17 participants |
| Docetaxel | Response Rate Per RECIST 1.1 Criteria | Progressive Disease | 17 participants |
| Docetaxel | Response Rate Per RECIST 1.1 Criteria | Not Assessed | 5 participants |
| Docetaxel Plus Suramin | Response Rate Per RECIST 1.1 Criteria | Not Assessed | 1 participants |
| Docetaxel Plus Suramin | Response Rate Per RECIST 1.1 Criteria | Partial Response | 3 participants |
| Docetaxel Plus Suramin | Response Rate Per RECIST 1.1 Criteria | Progressive Disease | 25 participants |
| Docetaxel Plus Suramin | Response Rate Per RECIST 1.1 Criteria | Stable Disease | 11 participants |