Nab-Paclitaxel With Gemcitabine for Relapsed Small Cell Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Study of Nab-Paclitaxel With Gemcitabine for Relapsed Small Cell Cancer or Those With Progression on First Line Therapy

Conditions
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Small Cell Lung Cancer (SCLC)

Intervention / Treatment
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* Drug: Nab-paclitaxel
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Age ≥18 years old, both male and female 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. ECOG performance status 0-2 Patients must have at least one measurable lesion as defined per RECIST 1.1 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). 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. 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. 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. Patients must be willing and able to sign informed consent for themselves 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. 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 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. 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 Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complication of study therapy 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]). Psychiatric disorder which, per treating physician discretion, may preclude compliance 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. 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. Pre-existing peripheral neuropathy > Grade 1 (using CTCAE v 4.3 criteria) Received any prior treatment with any taxane (docetaxel or paclitaxel) for small cell lung cancer. History of allergy or hypersensitivity to albumin-bound paclitaxel, or gemcitabine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nab-Paclitaxel with Gemcitabine<br>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 | Drug: Nab-paclitaxel<br>* Nab-paclitaxel 100 mg/m2, day 1 and day 8 of a 21-day cycle<br>* Other names: albumin-bound paclitaxel; paclitaxel protein-bound particles for injectable suspension (albumin-bound); Nab-paclitaxel Brand name: Abraxane ®;Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m2, day 1 and day 8 of a 21-day cycle<br>* Other names: Generic name: gemcitabine; Brand name: Gemzar ®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years) | 
| 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. | Patients will be evaluated every 2 cycles until progression or off treatment (up to 3 years) | 
| 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. | Patients will be evaluated every 3 months until death or study completion (up to 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abraxane, Albumin-bound Paclitaxel, SCLC, Gemzar