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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Chicago
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT01803269
First received: February 27, 2013
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Extensive Stage Small Cell Lung Cancer
Recurrent Small Cell Lung Cancer
Drug: topotecan hydrochloride
Drug: cyclodextrin-based polymer-camptothecin CRLX101
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of IV Topotecan Versus CRLX101 in the Second Line Treatment of Recurrent Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • PFS [ Time Frame: From randomization to time of progression or death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated in the two treatment groups by the Kaplan-Meier method and compared using a stratified logrank test. Ninety-percent confidence intervals for median PFS time in each arm will be calculated using the method of Brookmeyer and Crowley.


Secondary Outcome Measures:
  • Response rates according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Cohort A) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Compared between the two arms using Fisher's exact test and 95% confidence intervals will be generated for each group.

  • Continuous change in tumor size (Cohort A) [ Time Frame: Up to 56 days ] [ Designated as safety issue: No ]
    A two-sample t test will also be performed comparing the change in tumor size from baseline to the end of cycle two measured on a continuous scale (sum of longest diameters of target lesions).

  • Overall survival (Cohort A) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Analyzed using Kaplan-Meier estimates, stratified logrank tests and Cox regression modeling.

  • Frequency of reported side effects [ Time Frame: Up to 2 years after completion of study treatment ] [ Designated as safety issue: Yes ]
    Summarized by type and grade for each arm and compared using Fisher's exact test (dichotomized at grade 3 or higher) or via proportional odds models using the 0-5 grade scale.

  • PFS (Cohort B) [ Time Frame: From randomization to time of progression or death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • OS (Cohort B) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Response rate according to RECIST version 1.1 (Cohort B) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Reported along with a 90% confidence interval.


Estimated Enrollment: 156
Study Start Date: January 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Experimental: 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.
Drug: cyclodextrin-based polymer-camptothecin CRLX101
Given IV
Other Names:
  • CRLX101
  • cyclodextrin-based polymer-camptothecin IT-101
  • IT-101

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01803269

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Ravi Salgia    773-834-7424    rsalgia@medicine.bsd.uchicago.edu   
Principal Investigator: Ravi Salgia         
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Ravi Salgia University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01803269     History of Changes
Other Study ID Numbers: 12-1726, NCI-2013-00402
Study First Received: February 27, 2013
Last Updated: March 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Camptothecin
Topotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014