A Randomized Phase II Study of IV Topotecan Versus CRLX101 in the Second Line Treatment of Recurrent Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- topotecan hydrochloride
- Conditions
- Extensive Stage Small Cell Lung Cancer
- Sponsor
- University of Chicago
- Enrollment
- 29
- Locations
- 5
- Primary Endpoint
- Progression-free Survival
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Arm A (topotecan hydrochloride)
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.
Intervention: topotecan hydrochloride
Arm B (CRLX101)
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.
Intervention: cyclodextrin-based polymer-camptothecin CRLX101
Outcomes
Primary Outcomes
Progression-free Survival
Time Frame: 12 months
Time from enrollment to disease progression or death from any cause
Secondary Outcomes
- Continuous Change in Tumor Size.(Up to 56 days)
- Overall Survival(Up to 3 years)
- Response Rates According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Cohort A)(Up to 2 years)
- Frequency of Reported Side Effects(Up to 3 years after completion of study treatment)