Small Cell Lung Cancer (SCLC)
Conditions
Keywords
Abraxane, Albumin-bound Paclitaxel, SCLC, Gemzar
Brief summary
The purpose of this research study is to see if Abraxane and Gemcitabine given together will be effective in treating small cell cancer that has progressed after one line of treatment.
Detailed description
This study is designed as a second-line therapy for patients with histologically or cytologically confirmed small cell lung cancer or small cell cancer from other organs or poorly differentiated neuroendocrine tumors that are treated like small cell cancer. This study is for patients with metastatic or recurrent disease. Eligible patients will receive Nab-Paclitaxel (Abraxane), 100 mg/m2, IV over 30 minutes on Days 1 and 8 of a 21-day cycle followed by Gemcitabine, 1000 mg/m2, IV over 30 minutes on Days 1 and 8 of a 21-day cycle. Participants can continue receiving Nab-Paclitaxel and Gemcitabine until disease progression, unacceptable toxicity or withdrawal from the study. Tumor measurements will be done every 2 cycles.
Interventions
DRUGNab-paclitaxel
Nab-paclitaxel 100 mg/m2, day 1 and day 8 of a 21-day cycle
DRUGGemcitabine
Gemcitabine 1000 mg/m2, day 1 and day 8 of a 21-day cycle
Sponsors
Celgene Corporation
Muhammad Furqan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years old, both male and female 2. Histologically or cytologically confirmed SCLC SCLC or small cell cancer from other organs or poorly differentiated neuroendocrine tumors that are treated like small cell cancer. This study is for patients with metastatic or recurrent disease. 3. ECOG performance status 0-2 4. Patients must have at least one measurable lesion as defined per RECIST 1.1 5. Progression during or after prior first line chemotherapy. Prior maintenance therapy, targeted therapy and immunotherapy are allowed. Prior use of Rovalpituzumab or other ADC agent is allowed. Immunotherapy or targeted therapy if used as 2nd line therapy will not be considered as second line therapy as these are not true chemotherapeutic agents. Patients treated with definitive chemo-radiation will be eligible if they progressed within a year of definitive therapy (as definitive therapy will be considered 1st line therapy for these patients). 6. Before study therapy, a minimum of 21 days must have elapsed since any prior chemotherapy and 2 weeks from the last dose of prior targeted or immunotherapy. 7. Prior definitive XRT is allowed if it has been 2 weeks since the end of definitive XRT. For palliative XRT, protocol-specified treatment can begin at minimum 48 hours after completion of radiation. Lesions within the XRT field can only be used as target lesions if definite progression has been demonstrated since the completion of radiation. 8. Adequate major organ function including the following: * Hematologic function: Absolute neutrophil count (ANC) ≥ 1800 /mm3, platelet count ≥ 100,000/mm3, and Hgb ≥ 9.0 gm/dl. * Hepatic function: bilirubin ≤ 1.5 x ULN, AST and ALT levels ≤ 2.5 x ULN. If liver metastases are present, then AST and ALT ≤ 5 x ULN. * Renal function: serum creatinine ≤ 1.5 x ULN. 9. Patients must be willing and able to sign informed consent for themselves 10. If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device \[IUD\], birth control pills, or barrier device) during and for 6 months after trial. If male, use of an approved contraceptive method during the study and 6 months afterwards. Females with childbearing potential must have a urine negative hCG test within 7 days prior to the study therapy. Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy \[the surgical removal of the uterus\] or bilateral oophorectomy \[the surgical removal of both ovaries\] or (2) has not been naturally postmenopausal for at least 24 consecutive months \[i.e., has had menses at any time during the preceding 24 consecutive months\]) must: Either commit to true abstinence\* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting IP therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations following the last dose of IP; and Have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, as per clinical judgement of the investigator, and after the end of study therapy. This applies even if the subject practices true abstinence\* from heterosexual contact. 11. Male subjects must practice true abstinence\* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy. * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\].
Exclusion criteria
1. Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects: * Pregnant women * Nursing women * Men or women of childbearing potential, who are unwilling to employ adequate contraception as determined by treating physician, while on this study and for 6 months after the end of treatment with the study drugs. 2. History of the following within the prior 6 months: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant ECG abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder 3. Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complication of study therapy 4. History of other invasive malignancy that is currently active and/or has been treated within 12 months prior to enrollment (notable exceptions include: basal cell carcinoma, squamous cell carcinoma of the skin, localized prostate cancer, in situe carcinomas of the cervix and breast, and superficial bladder cancers \[non-muscle invasive\]). 5. Psychiatric disorder which, per treating physician discretion, may preclude compliance 6. Major surgery in the last two weeks of starting study therapy. This does not include procedures like biopsy (needle or excisional) or port placement as these are not considered as major surgery. 7. Individuals with the presence of symptomatic CNS metastasis requiring radiation, surgery, or ongoing use of corticosteroids. Untreated or brain metastasis causing any symptoms. Treated brain metastasis must be stable for 4 weeks prior to first dose of study drug and not require steroids for at least 7 days prior to study treatment. 8. Pre-existing peripheral neuropathy \> Grade 1 (using CTCAE v 4.3 criteria) 9. Received any prior treatment with any taxane (docetaxel or paclitaxel) for small cell lung cancer. 10. History of allergy or hypersensitivity to albumin-bound paclitaxel, or gemcitabine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years) | Overall response rate is defined as the percentage of patients with a confirmed complete or partial response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scan: Complete response (CR) is the disappearance of all target lesions. Partial Response (PR), is at least a ≥ 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum of the longest diameter (LD). Progression of disease (PD) is at least a ≥ 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and as defined by RECIST v1.1 guidelines. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years) | Time to progression is defined as the time from treatment initiation to the date of first documentation of disease progression per RECIST v1.1. Otherwise, patients are censored at last radiographic assessment for progression. |
| Progression-Free Survival | Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years) | Progression-free survival is defined as the time from treatment initiation to the date of first documentation of disease progression or death due to any cause. Otherwise, patients are censored at the date of last radiographic assessment for progression. |
| Overall Survival | Patients will be evaluated every 3 months until death or study completion (up to 3 years) | Overall survival is defined as the time from treatment initiation to death due to any cause. Patients still alive are censored at last date known to be alive. |
Countries
United States
Participant flow
Pre-assignment details
Treatment began following screening and within 14 days after screening, if patient is eligible and completed all required testing including medical history, physical exam including performance status, blood samples, pregnancy test, and tumor assessment done by computerized tomography (CT) scan, Chest X-Ray (CXR), or Magnetic Resonance Imaging (MRI).
Participants by arm
| Arm | Count |
|---|---|
| Nab-Paclitaxel With Gemcitabine Nab-paclitaxel 100 mg/m2, day 1 and day 8 of a 21-day cycle; Gemcitabine 1000 mg/m2, day 1 and day 8 of a 21-day cycle | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 30 |
Baseline characteristics
| Characteristic | Nab-Paclitaxel With Gemcitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 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 | 0 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 | 32 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 31 / 32 |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 14 / 32 |
Outcome results
Primary
Overall Response Rate
Overall response rate is defined as the percentage of patients with a confirmed complete or partial response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scan: Complete response (CR) is the disappearance of all target lesions. Partial Response (PR), is at least a ≥ 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum of the longest diameter (LD). Progression of disease (PD) is at least a ≥ 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and as defined by RECIST v1.1 guidelines. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Time frame: Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nab-Paclitaxel With Gemcitabine | Overall Response Rate | Complete Response | 0 Participants |
| Nab-Paclitaxel With Gemcitabine | Overall Response Rate | Partial Response | 9 Participants |
| Nab-Paclitaxel With Gemcitabine | Overall Response Rate | Progressive Disease | 7 Participants |
| Nab-Paclitaxel With Gemcitabine | Overall Response Rate | Stable Disease | 16 Participants |
Secondary
Overall Survival
Overall survival is defined as the time from treatment initiation to death due to any cause. Patients still alive are censored at last date known to be alive.
Time frame: Patients will be evaluated every 3 months until death or study completion (up to 3 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel With Gemcitabine | Overall Survival | 9.3 months |
Secondary
Progression-Free Survival
Progression-free survival is defined as the time from treatment initiation to the date of first documentation of disease progression or death due to any cause. Otherwise, patients are censored at the date of last radiographic assessment for progression.
Time frame: Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel With Gemcitabine | Progression-Free Survival | 2.9 months |
Secondary
Time to Progression
Time to progression is defined as the time from treatment initiation to the date of first documentation of disease progression per RECIST v1.1. Otherwise, patients are censored at last radiographic assessment for progression.
Time frame: Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel With Gemcitabine | Time to Progression | 2.9 months |