Topotecan Hydrochloride and Doxorubicin Hydrochloride in Treating Patients With Small Cell Lung Cancer That Has Relapsed or Not Responded to Treatment

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Nebraska
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Apar Kishor Ganti, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT00856037
First received: March 4, 2009
Last updated: October 8, 2013
Last verified: October 2013

March 4, 2009
October 8, 2013
February 2009
December 2014   (final data collection date for primary outcome measure)
  • Safety and efficacy of this regimen as assessed by the maximum tolerated dose (MTD) of the next lowest dose level below where greater than or equal to 2/3 or 3/6 patients experience dose limiting toxicities (DLT) in cohorts of 5 different doses [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]
  • DLT of topotecan hydrochloride administered in combination with doxorubicin hydrochloride as assessed by the MTD of the next lowest dose level below where greater than or equal to 2/3 or 3/6 patients experience DLT in cohorts of 5 different doses [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]
  • Safety and efficacy of this regimen by RECIST criteria [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity of topotecan hydrochloride administered in combination with doxorubicin hydrochloride [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00856037 on ClinicalTrials.gov Archive Site
Changes in topoisomerase I and II levels [ Time Frame: From baseline to week 16 ] [ Designated as safety issue: No ]
The changes over time will be described and correlated with hematological toxicity and efficacy. Mean change and standard deviation over time will be computed and when possible change in topoisomerase levels over time will be compared between patients developing grade 4 hematological toxicities versus others (no toxicity or grades 1-3) or between patients developing grades 3-4 non-hematological toxicities versus others (no toxicity or grades 1-2) or between patients who responded (complete response, partial response, stable disease) versus no response or progressed using non-parametric tests.
  • Correlation of topoisomerase I and II levels in peripheral blood with the presence or absence of grades 3 and 4 hematological toxicity [ Designated as safety issue: Yes ]
  • Correlation of topoisomerase I and II levels in peripheral blood with efficacy [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Topotecan Hydrochloride and Doxorubicin Hydrochloride in Treating Patients With Small Cell Lung Cancer That Has Relapsed or Not Responded to Treatment
A Phase I Study of Weekly Doxorubicin and Oral Topotecan for Patients With Relapsed or Refractory Small Cell Lung Cancer (SCLC)

This phase I trial is studying the side effects and best dose of topotecan hydrochloride when given together with doxorubicin hydrochloride in treating patients with small cell lung cancer (SCLC) that has relapsed or not responded to treatment. Drugs used in chemotherapy, such as topotecan hydrochloride and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Doxorubicin hydrochloride may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. Evaluate the safety and efficacy, in terms of clinical disease benefit, (complete or partial response and stable disease with stable or improved quality of life scores) of combination of oral topotecan (topotecan hydrochloride) when given with weekly doxorubicin (doxorubicin hydrochloride) in patients with SCLC.

II. Determine the dose limiting toxicity of oral topotecan when given with weekly doxorubicin in patients with SCLC.

SECONDARY OBJECTIVES:

I. Estimate topoisomerase I and II levels in peripheral blood mononuclear cells and correlate with presence or absence of grades 3 and 4 hematological toxicity.

II. Estimate topoisomerase I and II levels in peripheral blood mononuclear cells and correlate with efficacy.

OUTLINE: This is a dose-escalation study of topotecan hydrochloride.

Patients receive doxorubicin hydrochloride intravenously (IV) weekly beginning on day 6 in weeks 1-15. Patients also receive topotecan hydrochloride orally (PO) on days 1-5 in weeks 1, 4, 7, 10, and 13 in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, and at weeks 7 and 16 to measure topoisomerase I and II levels. Patients also complete the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life questionnaire at baseline, and at weeks 7 and 16.

After completion of study treatment, patients are followed up every 2 months.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Recurrent Small Cell Lung Cancer
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: topotecan hydrochloride
    Given PO
    Other Names:
    • hycamptamine
    • Hycamtin
    • SKF S-104864-A
    • TOPO
  • Procedure: laboratory biomarker analysis
    Correlative studies
  • Procedure: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
Experimental: Treatment (doxorubicin hydrochloride, topotecan hydrochloride)

Patients receive doxorubicin hydrochloride IV weekly beginning on day 6 in weeks 1-15. Patients also receive topotecan hydrochloride PO on days 1-5 in weeks 1, 4, 7, 10, and 13 in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, and at weeks 7 and 16 to measure topoisomerase I and II levels. Patients also complete the FACT-L quality of life questionnaire at baseline, and at weeks 7 and 16.

Interventions:
  • Drug: doxorubicin hydrochloride
  • Drug: topotecan hydrochloride
  • Procedure: laboratory biomarker analysis
  • Procedure: quality-of-life assessment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
18
Not Provided
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Pathologically proven diagnosis of SCLC
  • Have received at least one prior chemotherapy regimen for SCLC
  • Primarily refractory or relapsed disease
  • Measurable disease in 2 dimensions on imaging studies performed within 4 weeks of starting treatment
  • Greater than 2 weeks since last treatment (chemotherapy or radiation) provided subject has recovered from side effects of treatment prior to the study
  • Karnofsky score >= 70 (Eastern Cooperative Oncology Group [ECOG] 0-2)
  • No active secondary malignancy; patients with other prior malignancies will be included, provided they have been disease-free for at least five years
  • Patients with adequately treated basal cell or squamous cell carcinoma of the skin, adequately treated non-invasive carcinomas will be eligible
  • White blood cell (WBC) count >= 3,500/mm^3 , OR absolute neutrophil count (ANC) >= 1,500/ul and platelet count >= 100,000/mm^3 within 7 days prior to starting treatment
  • Serum creatinine less than 1.5 times the upper limits of normal within 7 days prior to starting treatment
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 1.5 times the upper limits of normal, serum alkaline phosphatase less than 2.5 times the upper limits of normal within 7 days prior to starting treatment in the absence of liver metastasis; in the presence of liver metastasis serum AST, ALT and alkaline phosphatase less than or equal to 5.0 times the upper limits of normal within 7 days prior to starting treatment
  • Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study; (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)
  • Non-pregnant and non-nursing; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on the study
  • Able to return for treatment and follow-up as specified in the protocol
  • Able to give informed consent

Exclusion Criteria:

  • Known hypersensitivity to any component of topotecan or doxorubicin or other required drugs in the study
  • Any co morbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol
  • Ejection fraction below the lower limit of normal (< 50%)
  • Uncontrolled intercurrent illnesses including, but not limited to unstable angina or uncontrolled cardiac arrhythmia, chronic liver disease, complete left bundle branch block, obligate use of a cardiac pacemaker, ST depression of > 1 mm in two or more leads and/or T wave inversions in two or more contiguous leads, congenital long QT syndrome, history of or presence of significant ventricular or atrial tachyarrhythmias, clinically significant resting bradycardia (< 50 beats per minute), corrected QT (QTc) > 480 ms on screening electrocardiogram that could jeopardize the patient's ability to receive the chemotherapy described in the protocol safely
  • Women who are pregnant (confirmed by a serum pregnancy test in females of reproductive potential) or breast-feeding; women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment (unless the subject or subject's partner(s) is sterile (i.e. women who have had a hysterectomy or have been post-menopausal for at least twelve consecutive months) or remain abstinent, men and women of reproductive potential must agree to use TWO of the following forms of birth control every time they have sex throughout the study and for up to 3 months following discontinuation of study drug: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicidal, intrauterine device (IUD), or surgical sterilization while participating in this study; hormonal birth control methods are not permitted
  • Inability to co-operate with the requirements of the protocol
Both
19 Years and older
No
United States
 
NCT00856037
508-08, NCI-2009-01308, P30CA036727
Yes
Apar Kishor Ganti, MD, University of Nebraska
University of Nebraska
National Cancer Institute (NCI)
Principal Investigator: Apar Ganti University of Nebraska
University of Nebraska
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP