Topotecan Hydrochloride or Cyclodextrin-Based Polymer-Camptothecin CRLX101 in Treating Patients With Recurrent Small Cell Lung Cancer

Study Overview
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Brief Summary
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This randomized phase II trial studies how well giving topotecan hydrochloride or cyclodextrin-based polymer-camptothecin CRLX101 works in treating patients with recurrent small cell lung cancer. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclodextrin-based polymer-camptothecin CRLX101 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet know whether topotecan hydrochloride is more effective than cyclodextrin-based polymer-camptothecin CRLX101 in treating patients with lung cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the effect of second-line treatment with CRLX101 (cyclodextrin-based polymer-camptothecin CRLX101) compared to intravenous (IV) topotecan hydrochloride (topotecan) on progression free survival (PFS) of patients with extensive-stage small cell lung cancer (ES-SCLC) sensitive to first-line platinum-based chemotherapy. II. To evaluate the effect of second-line treatment with CRLX101 on the three-month PFS rate of patients with ES-SCLC resistant to first-line platinum-based chemotherapy. SECONDARY OBJECTIVES: I. To evaluate the response rate of second-line treatment with CRLX101 in patients with ES-SCLC who are sensitive or resistant to first-line platinum-based chemotherapy. II. To evaluate the effect of second-line treatment with CRLX101 compared to IV topotecan on overall survival (OS) of patients with ES-SCLC sensitive to first-line platinum-based chemotherapy. III. To assess the overall survival of second-line treatment with CRLX101 in patients with ES-SCLC resistant to first-line platinum-based chemotherapy. IV. To assess the toxicity of second-line CRLX101 in patients sensitive or resistant to first-line platinum-based chemotherapy. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A (Sensitive Relapse): Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive topotecan hydrochloride intravenously (IV) over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive cyclodextrin-based polymer-camptothecin CRLX101 IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. COHORT B (Resistant Relapse): Patients receive cyclodextrin-based polymer-camptothecin CRLX101 as in Arm B Cohort A. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks and then every 3 months thereafter.

Official Title
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A Randomized Phase II Study of IV Topotecan Versus CRLX101 in the Second Line Treatment of Recurrent Small Cell Lung Cancer

Conditions
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Extensive Stage Small Cell Lung Cancer, Recurrent Small Cell Lung Cancer

Intervention / Treatment
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* Drug: topotecan hydrochloride
* Drug: cyclodextrin-based polymer-camptothecin CRLX101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed small cell lung cancer All patients must have extensive stage disease; extensive stage patients are defined as those patients with bilateral or contralateral supraclavicular adenopathy or contralateral hilar adenopathy or malignant pleural effusion or extrathoracic metastatic disease 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 spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam Patients must have been treated with 1 prior platinum-based (cisplatin or carboplatin) regimen; prior thoracic radiation for limited stage disease is allowed; patients must be at least 4 weeks since prior chemotherapy or radiation Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Life expectancy of greater than 3 months Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Total bilirubin within normal institutional limits Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal Creatinine within normal institutional limits OR Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Baseline imaging studies performed =< 28 days of study registration The effects of CRLX101 on the developing human fetus are unknown; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CRLX101 administration Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 2 weeks to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier Patients who have previously been treated with irinotecan or topotecan Patients who are receiving any other investigational agents Patients with uncontrolled brain metastases; patients with treated brain metastases must have stable neurologic status off of steroids and anticonvulsants for at least 2 weeks and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events History of allergic reactions attributed to compounds of similar chemical or biologic composition to CRLX101 or topotecan Patients with uncontrolled intercurrent 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 Previous or concurrent malignancy; exceptions: treated basal cell or squamous cell skin cancer, in situ cervical cancer, or lobular carcinoma in situ in one breast; or other cancer which the patient has been disease-free >= 5 years Pregnant women and women who are capable of reproduction but who will not agree to use adequate contraception prior to study entry and for the duration of study participation; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CRLX101 or topotecan, breastfeeding should be discontinued if the mother is treated with either agent Human immunodeficiency virus (HIV)-positive patients Patients with history of inflammatory bowel disease requiring therapy or patients with chronic diarrhea syndromes or paralytic ileus

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A (topotecan hydrochloride)<br>Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: topotecan hydrochloride<br>* Given IV<br>* Other names: TOPO;|
| Experimental: Arm B (CRLX101)<br>Patients receive cyclodextrin-based polymer-camptothecin CRLX10 cyclodextr1 IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: cyclodextrin-based polymer-camptothecin CRLX101<br>* Given IV<br>* Other names: IT-101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Time from enrollment to disease progression or death from any cause | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rates According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Cohort A) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Up to 2 years | 
| Continuous Change in Tumor Size. | Change in sum of longest diameters of all target lesions from baseline to end of cycle 2. | Up to 56 days | 
| Overall Survival | Time from enrollment until death from any cause | Up to 3 years | 
| Frequency of Reported Side Effects | Any adverse event regardless of grade or attribution | Up to 3 years after completion of study treatment |