The primary objective is the Objective tumor response rate (RECIST). Secondary objectives are: duration of overall response, time to tumor progression (TTP), progression free survival (PFS), overall survival, toxicity profile, incidence of…
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Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy:
The efficacy-evaluable population (primary efficacy population) includes all
patients who received at least one full cycle of amrubicin (Day 1-3
administration) and had at least one response assessment or discontinued before
having a response assessment due to rapid disease progression or death. Tumor
response will be assessed according to the RECIST criteria. Reassessment of
tumor will be done by the same methods used to establish baseline tumor
measurements. All responding patients (CR and PR) must have their response
confirmed no less than 4 weeks after the first documentation of response.
Safety:
All patients who received at least one dose of amrubicin on this study will be
considered evaluable for safety. Common Terminology Criteria for Adverse Events
(CTCAE) table, Version 3, will be used to grade toxicities. Duration and
treatment of toxicity will be recorded. The safety measures will be assessed on
an ongoing basis. The safety variables will be assessed by body system. Both
hematological and nonhematological adverse events that are considered
definitely, probably, or possibly drug-related will be monitored until
resolution.
Secondary outcome
Pharmacokinetics:
Secondary objectives of this study include determining the basic
pharmacokinetic parameters and between-subject variability of amrubicin and its
active metabolites at a dose of 40 mg/m2 given as an intravenous infusion over
approximately 5 minutes on Days 1, 2, and 3. Full PK data will be collected for
18 patients. Patients selected for full PK sampling will have blood samples
collected on Days 1 through 5 and Day 8 of Cycle 1.
Background summary
In Europe, platinum-based combination chemotherapy has become the standard for
the treatment of extensive disease SCLC (ED SCLC). Results of treatment remain
far from satisfactory since virtually all patients die of disease and long term
survivors are very few (under 10%).
Two studies in Japan with patients with refractory SCLC have shown the
anti-tumor activity of amrubicine when administered as monotherapy. In order to
confirm the promising results for refractory Japanese patients in US and
European patients, the same schedule used in Japan will be used in this trial.
Study objective
The primary objective is the Objective tumor response rate (RECIST).
Secondary objectives are: duration of overall response, time to tumor
progression (TTP), progression free survival (PFS), overall survival, toxicity
profile, incidence of cardiomyopathy, incidence of CNS progression,
pharmacokinetic parameters.
Study design
This is a Phase 2, open-label, non-randomized, multicenter, single-agent study
of amrubicin for the treatment of patients who have ED-SCLC that is considered
refractory to prior platinum-based first-line therapy.
Patient sample size determination is based on the Fleming Single-Stage Design
methodology. Efficacy will be measured by the overall response rate (complete
and partial responses). Amrubicin will be considered promising if the true
overall response rate is 18% or higher, and will be considered unworthy of
further investigation if the true overall response rate is 6% or less in this
refractory population.
Patient accrual will continue until at least 63 refractory patients receive at
least one full cycle of amrubicin (Day 1-3 administration) and either had the
Cycle 2 tumor assessment performed or had early tumor progression. If 7 or
fewer responses (CR + PR) are observed in this group of 63, the hypothesis that
the true response rate is less or equal to 6% cannot be rejected. If 8 or more
responses are achieved, the hypothesis that the true response rate is less than
or equal to 6% is rejected and this regimen will be considered worthy of
further testing. This design yields 0.90 probability of a positive result if
the true response rate is 18% or higher and 0.05 probability of a positive
result if the true response rate is 6% or lower.
Intervention
Patients will receive 40 mg/m2 amrubicin as a slow IV push or infusion over
approximately 5 minute once daily for 3 consecutive days starting on Day 1 of
every 21 day cycle.
Study burden and risks
Screening:·complete medical, surgical and prior chemotherapy history (including
all medications), Physical examination, Blood sample, Pregnancy test for women
of childbearing potential, 12-lead electrocardiogram and Urinalysis.
Radiographic measurement of the tumors will be done before start of treatment
and then every 6 weeks.
On Day 1: a physical examination, an ECG, Blood samples, questions any
medications the patient might be taking or have taken since the last visit and
side effects.
On each treatment day (Day 2-3):vital signs and patient will be asked about all
medications the patient might be taking or has taken since the last visit and
about side effects.
Days 8 and 15. blood sample, vital signs and the patient will be asked about
any medications the patient might be taking or has taken since your last visit
and about side effects.
Before treatment, after cycle 3 and cycle 6 (and thereafter every 2 cycles) a
echocardiogram or MUGA scan will be taken.
end-of-study: physical examination, vital signs, blood samples, ECG
electrocardiogram and the patient will be asked about any medications the
patient might be taking or has taken since your last visit and about side
effects.
For patients consenting to pharmacokinetic research extra blood samples will be
taken on days 1, 2, 3, 4, 5, 8 and also ECG will be taken.
For patients consenting to pharmacogenetic research, an extra blood sample will
be taken on Day 1 of start of the study.
2525 28th St Suite 200
Boulder, CO 80301
USA
2525 28th St Suite 200
Boulder, CO 80301
USA
Listed location countries
Age
Inclusion criteria
- Histological or cytological diagnosis of SCLC; extensive-disease (ED) at the time of study entry
- Refractory to first-line platinum-based chemotherapy (i.e., has received one prior platinum-based chemotherapy regimen) defined as one of the following:
a. Best response to first-line chemotherapy is radiographically documented progression (refractory disease)
b. Best response to first-line chemotherapy is radiographically documented response or stable disease, with subsequent documented progression during continuing chemotherapy (resistant relapse)
c. Documented progression within 90 days of completion of first-line chemotherapy (last dose of chemotherapy), regardless of best response to treatment (resistant relapse)
- At least 18 years of age
- ECOG Performance Status of 0, 1, or 2
- Measurable disease defined by RECIST criteria:
a. Measurable disease: The presence of at least one measurable lesion. If only one lesion is present, the neoplastic nature of the disease site should be confirmed by histology and/or cytology
b. Measurable lesion: Lesions that can be accurately measured in at least one dimension with the longest diameter ><= 20 mm using conventional techniques or ><= 10 mm using spiral CT scans. CT (including spiral CT) scans and MRI are the preferred methods of measurement; however, chest x-rays are acceptable if the lesions are clearly defined and surrounded by aerated lung. Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes). For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion is required.
- Adequate organ function including the following:
a. Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ><= 1500 cells/uL, platelet count ><= 100,000 cells/uL and hemoglobin ><= 9 g/dL
b. Hepatic: bilirubin <<= 1.5 X ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <<= 3.0 X ULN.
c. Renal: serum creatinine < 2.0 mg/dL or calculated creatinine clearance > 60 mL/min
d. Cardiac: Left ventricular ejection fraction (LVEF) ><= 50% by MUGA or echocardiography (intra-patient reassessment of LVEF should be performed via the same method throughout the study).
- Negative serum pregnancy test at the time of enrollment for women of child-bearing potential. For men and women of child-producing potential, use of effective contraceptive methods during the study.
- Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments
Exclusion criteria
- Pregnant or nursing women
- Chest radiotherapy within the previous 28 days or other radiotherapy within the previous 14 days. Recovery from the acute toxic effects of radiation required prior to study enrollment. Measurable lesions that have been previously irradiated must be enlarging to be considered target lesions. Prior radiation therapy allowed to < 25% of the bone marrow.
- More than 1 prior chemotherapy regimen for SCLC.
- Prior anthracycline treatment.
- treatment with any investigational agent within 28 days or standard chemotherapy with 21 days prior to first dose. patients must have recovered from all acute adverse events of prior therapies, excluding alopecia
- Patients with second primary malignancy (except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 2 years previously with surgery and/or radiotherapy and no evidence of recurrence since that time).
- Concurrent severe or uncontrolled medical disease (i.e., active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study.
- Symptomatic central nervous system metastases. Patients with asymptomatic brain metastases are allowed. The patient must be stable after radiotherapy for >= 2 weeks and off corticosteroids for >= 1 week.
- History of interstitial lung disease or pulmonary fibrosis.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-004785-14-NL |
| CCMO | NL14576.029.06 |