Non-small Cell Lung Cancer
Conditions
Keywords
NSCLC, suramin, lung cancer, chemotherapy
Brief summary
The purpose of this study is to evaluate the benefit of adding suramin at a non-cytotoxic dose to carboplatin and docetaxel regimen in the treatment of chemo-naïve patients with non-small cell lung cancer.
Detailed description
The primary objective is to determine the progression free survival for patients with stage III B with malignant pleural effusion or Stage IV NSCLC treated with docetaxel and carboplatin with or without suramin. The secondary objectives are to compare median overall survival rate, compare overall response rate of patients in both arms, assess toxicity of suramin with docetaxel and carboplatin, determine whether pre-treatment bFGF levels correlate with survival, to determine whether survival benefit from suramin is associated with M phase entry in peripheral blood lymphocytes, and to determine whether adding suramin to docetaxel and carboplatin produces greater survival benefits in African-American patients.
Interventions
DRUGSuramin Drug:Docetaxel Drug: Carboplatin
Suramin dosage will be determined by nomogram and administered over 30 minutes. Suramin is followed by docetaxel (56 mg/m2, administered over 1 hour), followed by carboplatin (dosage calculated by Calvert equation to have a target AUC of 6, administered over 1 hour).
DRUGPlacebo Drug: Docetaxel Drug: Carboplatin
Placebo (100 ml of 0.9% sodium chloride or 5% dextrose in water) will be administered over 30 minutes, followed by docetaxel (75 mg/m2, administered over 1 hour), followed by carboplatin (dose calculated by Calvert equation to have a target AUC of 6, administered over 1 hour).
Sponsors
Optimum Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically proven on-small cell lung cancer (NSCLC), including squamous cell carcinoma. * Newly-diagnosed stage IIIB with malignant pleural effusion, stage IV or recurrent disease. * Known central nervous system metastases if patients are asymptomatic and have completed whole brain or stereotactic radiation at least 2 weeks prior or surgery at least 4 weeks prior to starting treatment on this protocol. Must be off dexamethasone at the time of starting treatment. * Must have completed radiotherapy at least two weeks prior to registration. Prior radiation therapy is eligible if patient has a measurable lesion that has not been irradiated. * Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (RECIST criteria). * Lesions that are not considered measurable include the following: * Bone lesions * Leptomeningeal disease * Ascites * Pleural/pericardial effusion * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * Tumor lesions situated in a previously irradiated area * ECOG performance status of 0-1. * Life expectancy ≥ 3 months. * Adequate bone marrow function, absolute neutrophil count ≥1,500/mm3, hemoglobin ≥9.9 gm/dl, and platelet count ≥100,000/mm3. * Adequate liver function defined as bilirubin ≤ 1x upper level of the institutional normal (ULIN). AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used. See protocol. * Must have adequate renal function defined as serum creatinine ≤ 2.0 mg/dl or calculated creatinine clearance ≥ 60 ml/min for patients with creatinine levels above 2.0 mg/dl. * Must have recovered from uncontrolled intercurrent illness, including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia. * Use of adequate contraception (hormonal or barrier method of birth control) for the duration of study participation and continued for at least three months after completing treatment. Non-pregnant status will be determined in all women of childbearing potential. * Age \> 18. * Patients must have given written informed consent. * Entry to this study is open to both men and women and to all racial and ethnic subgroups. The goal is to accrue a minimum of 44 patients of African-American ancestry and a maximum of 120 non-African-American patients. Classification of patient race and ancestry will be based on patient's self-identification on the consent form for the clinical trial.
Exclusion criteria
* History of severe hypersensitivity reaction to Docetaxel or other drugs formulated with polysorbate 80. * Grade 3 or 4 neuropathy. * Women who are pregnant or breast-feeding. * Prior chemotherapy or biologic therapy (e.g., erlotinib) for NSCLC including neoadjuvant or adjuvant chemotherapy. * Currently active second malignancy other than non-melanoma skin cancer. Currently active malignancy does not include prior malignancy treated with therapy and considered to have less than 30% risk of relapse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival for Participants With Stage IIIB/IV NSCLC Per RECIST Criteria | Patients will be followed every 2 months for the first 6 months following the last cycle of treatment, every three months for the next year, and every 6 months thereafter. | Insufficient data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival of Participants | First treatment date to date of death | Insufficient Data |
| Overall Response Rate (Complete Response + Partial Response) of Participants | Tumor assessment at every other cycle | Insufficient data |
| Toxicity of Combination of Non-cytotoxic Suramin With Docetaxel and Carboplatin. | Day 1 of each cycle; end of treatment visit; at follow-up. | Insufficient data. |
| Pre-treatment bFGF Levels Correlation With Survival. | Before first treatment | Insufficient data. |
| Survival Benefit From Non-cytotoxic Suramin Association With Reduced M-phase Entry in Peripheral Blood Lymphocytes | Randomization date | Insufficient data. |
| To Determine Whether Adding Non-cytotoxic Suramin to Docetaxel and Carboplatin Produces Survival Benefits in African-American Patients. | Randomization date to date of death | Insufficient data. |
| To Determine Whether Adding Non-cytotoxic Suramin to Docetaxel and Carboplatin Produces Greater Survival Benefits in African-American Patients Compared to Non-African-American Patients. | Randomization date to date of death | Insufficient data. |
Countries
United States
Participant flow
Recruitment details
A total of 164 subjects were expected to be enrolled in this study; however, only a total of 14 subjects were enrolled at two active sites. Site 001 (Virginia Commonwealth University) enrolled 4 subjects and site 002 (Cook County) enrolled 10 subjects for a total of 14 subjects.
Participants by arm
| Arm | Count |
|---|---|
| Suramin This group will receive the combination of non-cytotoxic suramin with docetaxel and carboplatin.
Suramin + Docetaxel + Carboplatin: Suramin dosage will be determined by nomogram and administered over 30 minutes. Suramin is followed by docetaxel (56 mg/m2, administered over 1 hour), followed by carboplatin (dosage calculated by Calvert equation to have a target AUC of 6, administered over 1 hour). | 8 |
| Standard of Care This group will receive placebo with docetaxel and carboplatin.
Placebo + Docetaxel + Carboplatin: Placebo (100 ml of 0.9% sodium chloride or 5% dextrose in water) will be administered over 30 minutes, followed by docetaxel (75 mg/m2, administered over 1 hour), followed by carboplatin (dose calculated by Calvert equation to have a target AUC of 6, administered over 1 hour). | 6 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Tumor Progression | 2 | 2 |
Baseline characteristics
| Characteristic | Suramin | Total | Standard of Care |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 7 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 7 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 14 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Non-small cell lung cancer (NSCLC) Disease Stage at Entry IIIB | 1 participants | 1 participants | 0 participants |
| Non-small cell lung cancer (NSCLC) Disease Stage at Entry IV | 7 participants | 13 participants | 6 participants |
| Non-small cell lung cancer (NSCLC) Disease Type Nonsquamous | 6 participants | 10 participants | 4 participants |
| Non-small cell lung cancer (NSCLC) Disease Type Squamous | 2 participants | 4 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 6 / 6 |
| serious Total, serious adverse events | 3 / 8 | 0 / 6 |
Outcome results
Primary
Progression-free Survival for Participants With Stage IIIB/IV NSCLC Per RECIST Criteria
Insufficient data
Time frame: Patients will be followed every 2 months for the first 6 months following the last cycle of treatment, every three months for the next year, and every 6 months thereafter.
Population: Because 6 of 14 participants were lost to follow up before progression, analysis was not performed.
Secondary
Overall Response Rate (Complete Response + Partial Response) of Participants
Insufficient data
Time frame: Tumor assessment at every other cycle
Population: Because 6 of 14 participants were lost to follow up before progression, analysis was not performed.
Secondary
Overall Survival of Participants
Insufficient Data
Time frame: First treatment date to date of death
Population: Because 6 of 14 participants were lost to follow up before progression, analysis was not performed.
Secondary
Pre-treatment bFGF Levels Correlation With Survival.
Insufficient data.
Time frame: Before first treatment
Population: Because 6 of 14 participants were lost to follow up before progression, analysis was not performed.
Secondary
Survival Benefit From Non-cytotoxic Suramin Association With Reduced M-phase Entry in Peripheral Blood Lymphocytes
Insufficient data.
Time frame: Randomization date
Population: Because 6 of 14 participants were lost to follow up before progression, analysis was not performed.
Secondary
To Determine Whether Adding Non-cytotoxic Suramin to Docetaxel and Carboplatin Produces Greater Survival Benefits in African-American Patients Compared to Non-African-American Patients.
Insufficient data.
Time frame: Randomization date to date of death
Population: Because 6 of 14 participants were lost to follow up before progression, analysis was not performed.
Secondary
To Determine Whether Adding Non-cytotoxic Suramin to Docetaxel and Carboplatin Produces Survival Benefits in African-American Patients.
Insufficient data.
Time frame: Randomization date to date of death
Population: Because 6 of 14 participants were lost to follow up before progression, analysis was not performed.
Secondary
Toxicity of Combination of Non-cytotoxic Suramin With Docetaxel and Carboplatin.
Insufficient data.
Time frame: Day 1 of each cycle; end of treatment visit; at follow-up.
Population: Because 6 of 14 participants were lost to follow up before progression, analysis was not performed.