Recurrent Small Cell Lung CarcinomaPhase 1NCT00856037
Topotecan Hydrochloride and Doxorubicin Hydrochloride in Treating Relapsed or Refractory Small Cell Lung Cancer
A Phase 1 study testing Doxorubicin Hydrochloride, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Recurrent Small Cell Lung Carcinoma, run by University of Nebraska at 1 site in United States.
Trial summary
This phase I trial studies 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 come back after a period of improvement (relapsed) or has not responded to treatment (refractory). Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Recurrent Small Cell Lung Carcinoma
- What is being tested?
- Doxorubicin Hydrochloride, Laboratory Biomarker Analysis and Quality-of-Life Assessment
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Feb 2009to 1 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically proven diagnosis of small cell lung cancer (SCLC)
- Have received at least one prior chemotherapy regimen for SCLC
- Primarily refractory or relapsed disease
- Measurable or evaluable 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)
Show all 18Show fewer
- 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 within 7 days prior to starting treatment, OR
- Absolute neutrophil count (ANC) >= 1,500/ul within 7 days prior to starting treatment
- 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 within 7 days prior to starting treatment in the absence of liver metastasis; in the presence of liver metastasis serum AST and ALT less than or equal to 5.0 times the upper limits of normal within 7 days prior to starting treatment
- 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 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: 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 studies 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 come back after a period of improvement (relapsed) or has not responded to treatment (refractory). 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, by stopping them from dividing, or by stopping them from spreading. Doxorubicin hydrochloride may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving topotecan hydrochloride and doxorubicin hydrochloride may be a better treatment for small cell lung cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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) over 3-5 minutes on day 6 of course 1 and on days 6, 13, and 20 of courses 2-5. Patients also receive topotecan hydrochloride orally (PO) on days 1-5. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months.
- Conditions
- Recurrent Small Cell Lung Carcinoma
- Being tested
- Doxorubicin Hydrochloride, Laboratory Biomarker Analysis, Quality-of-Life Assessment, Topotecan Hydrochloride
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Topotecan HydrochlorideDrug
Also called Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (doxorubicin hydrochloride, topotecan hydrochloride) | Experimental | Patients receive doxorubicin hydrochloride IV over 3-5 minutes on day 6 of course 1 and on days 6, 13, and 20 of courses 2-5. Patients also receive topotecan hydrochloride PO on days 1-5. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Topotecan Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose defined as the next lowest dose level below where greater than or equal to 2/3 or 3/6 patients experience dose limiting toxicities in cohorts of 5 different doses by National Cancer Institute Common Toxicity Criteria version 3.0
The actual rates of dose limiting toxicities per dose cohort will be presented when applicable.
Measured: Up to 6 weeks (after 2 courses)
Secondary outcomes (3)
Changes in topoisomerase I and II levels in peripheral blood mononuclear cells
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.
Measured: Baseline to up to week 16
Overall response rate
complete or partial response and stable disease
Measured: Up to 15 weeks (after 5 courses)
Changes in quality of life levels
Measured by standard instruments and compared when possible between patients who responded versus nonresponders.
Measured: Up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2009 (estimated)
- Study start2 Feb 2009
- Primary completion1 Feb 2018
- Study completion1 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Apar Ganti, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00856037
- Sponsor's protocol ID
- 0508-08-FB
- Other IDs
- NCI-2009-01308, P30CA036727
- Status last verified
- Sep 2023
- First submitted
- 4 Mar 2009
- Last updated
- 26 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Weekly Doxorubicin and Oral Topotecan for Patients With Relapsed or Refractory Small Cell Lung Cancer (SCLC)
- ClinicalTrials.gov ID
- NCT00856037
- Acronym / sponsor ID
- 0508-08-FB
- Conditions
- Recurrent Small Cell Lung Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 2 Feb 2009 (actual)
- Primary completion
- 1 Feb 2018 (actual)
- Study completion
- 1 Feb 2018 (actual)
- First posted
- 5 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies 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 come back after a period of improvement (relapsed) or has not responded to treatment (refractory). 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, by stopping them from dividing, or by stopping them from spreading. Doxorubicin hydrochloride may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving topotecan hydrochloride and doxorubicin hydrochloride may be a better treatment for small cell lung cancer.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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) over 3-5 minutes on day 6 of course 1 and on days 6, 13, and 20 of courses 2-5. Patients also receive topotecan hydrochloride orally (PO) on days 1-5. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (doxorubicin hydrochloride, topotecan hydrochloride) | Experimental | Drug: Doxorubicin Hydrochloride, Other: Laboratory Biomarker Analysis, Other: Quality-of-Life Assessment, Drug: Topotecan HydrochloridePatients receive doxorubicin hydrochloride IV over 3-5 minutes on day 6 of course 1 and on days 6, 13, and 20 of courses 2-5. Patients also receive topotecan hydrochloride PO on days 1-5. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Pathologically proven diagnosis of small cell lung cancer (SCLC)
- Have received at least one prior chemotherapy regimen for SCLC
- Primarily refractory or relapsed disease
- Measurable or evaluable 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxorubicin HydrochlorideAlso: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, AdriamycinGiven IV | Drug | Treatment (doxorubicin hydrochloride, topotecan hydrochloride) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (doxorubicin hydrochloride, topotecan hydrochloride) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (doxorubicin hydrochloride, topotecan hydrochloride) |
| Topotecan HydrochlorideAlso: Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HClGiven PO | Drug | Treatment (doxorubicin hydrochloride, topotecan hydrochloride) |
Primary outcome
Maximum tolerated dose defined as the next lowest dose level below where greater than or equal to 2/3 or 3/6 patients experience dose limiting toxicities in cohorts of 5 different doses by National Cancer Institute Common Toxicity Criteria version 3.0
Time frame: Up to 6 weeks (after 2 courses)
The actual rates of dose limiting toxicities per dose cohort will be presented when applicable.
3 secondary outcomes
Changes in topoisomerase I and II levels in peripheral blood mononuclear cells
Time frame: Baseline to up to week 16
Overall response rate
Time frame: Up to 15 weeks (after 5 courses)
Changes in quality of life levels
Time frame: Up to 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Apar Ganti, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Doxorubicin Hydrochloride, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Recurrent Small Cell Lung Carcinoma, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose defined as the next lowest dose level below where greater than or equal to 2/3 or 3/6 patients experience dose limiting toxicities in cohorts of 5 different doses by National Cancer Institute Common Toxicity Criteria version 3.0 (time frame: Up to 6 weeks (after 2 courses)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2023.