Back to resultsPhase I Combination Ixabepilone + Cisplatin
Primary Purpose
Non Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Ixabepilone
Cisplatin
Ixabepilone
Cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Lung Cancer (NSCLC)
Eligibility Criteria
Escalation Phase Subjects: Primary solid tumor not curable by local measures such as surgery, radiation
Inclusion Criteria:
- Men and women age ≥ 18
Exclusion:
- More than 2 prior chemotherapy containing regimens for metastatic disease
- No prior exposure to cisplatin or ixabepilone
Expansion Phase Subjects: Advanced Non-small cell lung cancer
Inclusion Criteria:
- Men and women age ≥ 18
Exclusion:
- No prior chemotherapy-containing regimen for metastatic disease
- No prior exposure to cisplatin or ixabepilone
Sites / Locations
- Georgetown University Medical Center
- The Cancer Institute Of New Jersey
- Penn State Milton S. Hershey Medical Center
- Local Institution
- Local Institution
- Local Institution
- Local Institution
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Escalation and Expansion
Arm Description
Outcomes
Primary Outcome Measures
Participants Experiencing Dose Limiting Toxicity (DLT)
DLT=any of the following treatment-related events:Grade(Gr)3/4 diarrhea despite the use of adequate/maximal medical intervention and/or prophylaxis;other Gr3 or greater nonhematological toxicity requiring removal from further study therapy;delayed recovery from treatment-related toxicity delaying scheduled retreatment for >3 weeks;Gr4 neutropenia (absolute neutrophil count <500 cells/mm^3) for >=5 consecutive days or Gr3/4 neutropenia of any duration with sepsis or fever >38.5°C;thrombocytopenia <25,000 cells/mm^3 or bleeding requiring platelet transfusion. Grades defined in Outcome Measure 7.
Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of Cisplatin in Combination With Ixabepilone, 32 mg/m^2
The MTD is defined as the highest dose level in which dose limiting toxicities (DLTs) during the first 21 days of the first treatment cycle are observed in less than 1 out of 3 or less than 2 out of 6 treated subjects with at least 2 subjects experiencing DLT at the next higher dose level.
Secondary Outcome Measures
Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST)
Complete Response(CR):Disappearance of all clinical/radiological evidence of target lesions (TL) & all nontarget lesions (NTL) + no new lesions (NWL). Partial Response(PR):CR of TL + persistence of >=1 NTL (NonCR/NonPD) + no NWL; OR >=30% decrease in sum of longest diameter(LD) of all TL + CR or NonCR/NonPD in NTL + no NWL. Progressive Disease (PD):>=20% increase in sum of LD of TL regardless of NTL & NWL status; or unequivocal progression of NTL regardless of TL & NWL status; or NWL regardless of TL & NTL status. Stable Disease(SD): Neither PD nor PR in TL + CR or NonCR/NonPD in NTL + no NWL.
Percentage of Participants With Response
Response in participants with non-small cell lung cancer (NSCLC) was defined as the number of subjects in whose best response is partial response (PR) or complete response (CR) (see Outcome Measure 3 for definitions) divided by the total number of response evaluable subjects.
Duration of Response in Participants With Non-small Cell Lung Cancer (NSCLC)
The duration of response will be computed for all treated subjects whose best response is either partial response (PR) or complete response (CR). The duration of response is measured from the time (in months) measurement criteria are first met for PR or CR, whichever is recorded first, until the date of documented progressive disease or death. Subjects who neither relapse nor die will be censored on the date of their last tumor assessment.
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Per National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE)Version 3 Criteria
AE=any new untoward medical occurrence/worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical event that results in death, persistent/significant incapacity, drug dependency or abuse; is life-threatening, an important medical event, a congenital anomaly/birth defect; requires/prolongs inpatient hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment. Grade 1=Mild, 2=Moderate, 3=Severe/medically significant, 4=Life-threatening.
Number of Participants With Laboratory Abnormalities Per National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE)Version 3 Criteria
Grade (Gr) 1=Mild, 2=Moderate, 3=Severe/medically significant, 4=Life-threatening. Hemoglobin Gr1 <LLN - 10.0 g/dL; Gr2 <10.0 - 8.0 g/dL; Gr3 <8.0 - 6.5 g/dL; Gr4 <6.5 g/dL. White Blood Cell Count (WBC) Gr1 <lower limit of normal (LLN) - 3000/mm^3; Gr2 <3000 - 2000/mm^3; Gr3 <2000 - 1000/mm^3; Gr4 <1000/mm^3. Absolute Neutrophil Count (ANC) Gr 1 <LLN - 1500/mm^3; Gr 2 <1500 - 1000/mm^3; Gr3 <1000 - 500/mm^3; Gr 4 <500/mm^3. Platelets Gr1 <LLN - 75,000/mm^3; Gr2 <75,000 - 50,000/mm^3; Gr3 <50,000 - 25,000/mm^3; Gr4 <25,000/mm^3. Normal ranges vary by local laboratory.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00832117
Brief Title
Phase I Combination Ixabepilone + Cisplatin
Official Title
Phase 1 Study of Ixabepilone in Combination With Cisplatin in Subjects With Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
R-Pharm
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the highest dose of ixabepilone that can be given safely with cisplatin without causing severe or life-threatening side effects and for some patients with non-small cell lung cancer, the effects (good or bad) on your cancer will also be studied
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer
Keywords
Lung Cancer (NSCLC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Escalation and Expansion
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Ixabepilone
Other Intervention Name(s)
IXEMPRA®
Intervention Description
Escalation: Solution, intravenous (IV), 32-40 mg/m2, every 3 weeks, approximately 6 months
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Escalation: Solution, IV, 60-100 mg/m2, every 3 weeks, approximately 6 months
Intervention Type
Drug
Intervention Name(s)
Ixabepilone
Other Intervention Name(s)
IXEMPRA®
Intervention Description
Expansion: Solution, IV, 32 mg/m2, every 3 weeks, approximately 6 months
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Expansion: Solution, IV, 60-80 mg/m2, every 3 weeks, approximately 6 months
Primary Outcome Measure Information:
Title
Participants Experiencing Dose Limiting Toxicity (DLT)
Description
DLT=any of the following treatment-related events:Grade(Gr)3/4 diarrhea despite the use of adequate/maximal medical intervention and/or prophylaxis;other Gr3 or greater nonhematological toxicity requiring removal from further study therapy;delayed recovery from treatment-related toxicity delaying scheduled retreatment for >3 weeks;Gr4 neutropenia (absolute neutrophil count <500 cells/mm^3) for >=5 consecutive days or Gr3/4 neutropenia of any duration with sepsis or fever >38.5°C;thrombocytopenia <25,000 cells/mm^3 or bleeding requiring platelet transfusion. Grades defined in Outcome Measure 7.
Time Frame
Within the first 21 days of first cycle
Title
Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of Cisplatin in Combination With Ixabepilone, 32 mg/m^2
Description
The MTD is defined as the highest dose level in which dose limiting toxicities (DLTs) during the first 21 days of the first treatment cycle are observed in less than 1 out of 3 or less than 2 out of 6 treated subjects with at least 2 subjects experiencing DLT at the next higher dose level.
Time Frame
Within the first 21 days of first cycle
Secondary Outcome Measure Information:
Title
Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST)
Description
Complete Response(CR):Disappearance of all clinical/radiological evidence of target lesions (TL) & all nontarget lesions (NTL) + no new lesions (NWL). Partial Response(PR):CR of TL + persistence of >=1 NTL (NonCR/NonPD) + no NWL; OR >=30% decrease in sum of longest diameter(LD) of all TL + CR or NonCR/NonPD in NTL + no NWL. Progressive Disease (PD):>=20% increase in sum of LD of TL regardless of NTL & NWL status; or unequivocal progression of NTL regardless of TL & NWL status; or NWL regardless of TL & NTL status. Stable Disease(SD): Neither PD nor PR in TL + CR or NonCR/NonPD in NTL + no NWL.
Time Frame
At End-of-Treatment visit. Median time on study therapy was 18 weeks (range: 6-69 weeks) for ixa 32 mg/m^2+cis 60 mg/m^2 arm; 6 weeks (range: 3-18 weeks) for ixa 32mg/m^2+cis 80 mg/m^2 arm.
Title
Percentage of Participants With Response
Description
Response in participants with non-small cell lung cancer (NSCLC) was defined as the number of subjects in whose best response is partial response (PR) or complete response (CR) (see Outcome Measure 3 for definitions) divided by the total number of response evaluable subjects.
Time Frame
At End-of-Treatment visit. Median time on study therapy was 18 weeks (range: 6-69 weeks) for ixa 32 mg/m^2+cis 60 mg/m^2 arm; 6 weeks (range: 3-18 weeks) for ixa 32mg/m^2+cis 80 mg/m^2 arm.
Title
Duration of Response in Participants With Non-small Cell Lung Cancer (NSCLC)
Description
The duration of response will be computed for all treated subjects whose best response is either partial response (PR) or complete response (CR). The duration of response is measured from the time (in months) measurement criteria are first met for PR or CR, whichever is recorded first, until the date of documented progressive disease or death. Subjects who neither relapse nor die will be censored on the date of their last tumor assessment.
Time Frame
The duration of response is measured from the time (in months) measurement criteria are first met for PR or CR, whichever is recorded first, until the date of documented progressive disease or death. (Duration of study was approximately 21 months.)
Title
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Per National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE)Version 3 Criteria
Description
AE=any new untoward medical occurrence/worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical event that results in death, persistent/significant incapacity, drug dependency or abuse; is life-threatening, an important medical event, a congenital anomaly/birth defect; requires/prolongs inpatient hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment. Grade 1=Mild, 2=Moderate, 3=Severe/medically significant, 4=Life-threatening.
Time Frame
Assessed from the date of first dose until at least 30 days after the last dose of study drug. Median time on study therapy was 18 weeks (range: 6-69 weeks) for ixa 32 mg/m^2+cis 60 mg/m^2 arm; 6 weeks (range: 3-18 weeks) for ixa 32mg/m^2+cis 80 mg/m^2.
Title
Number of Participants With Laboratory Abnormalities Per National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE)Version 3 Criteria
Description
Grade (Gr) 1=Mild, 2=Moderate, 3=Severe/medically significant, 4=Life-threatening. Hemoglobin Gr1 <LLN - 10.0 g/dL; Gr2 <10.0 - 8.0 g/dL; Gr3 <8.0 - 6.5 g/dL; Gr4 <6.5 g/dL. White Blood Cell Count (WBC) Gr1 <lower limit of normal (LLN) - 3000/mm^3; Gr2 <3000 - 2000/mm^3; Gr3 <2000 - 1000/mm^3; Gr4 <1000/mm^3. Absolute Neutrophil Count (ANC) Gr 1 <LLN - 1500/mm^3; Gr 2 <1500 - 1000/mm^3; Gr3 <1000 - 500/mm^3; Gr 4 <500/mm^3. Platelets Gr1 <LLN - 75,000/mm^3; Gr2 <75,000 - 50,000/mm^3; Gr3 <50,000 - 25,000/mm^3; Gr4 <25,000/mm^3. Normal ranges vary by local laboratory.
Time Frame
Assessed at screening and weekly during treatment. Median time on study therapy was 18 weeks (range: 6-69 weeks) for ixa 32 mg/m^2+cis 60 mg/m^2 arm; 6 weeks (range: 3-18 weeks) for ixa 32mg/m^2+cis 80 mg/m^2.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Escalation Phase Subjects: Primary solid tumor not curable by local measures such as surgery, radiation
Inclusion Criteria:
Men and women age ≥ 18
Exclusion:
More than 2 prior chemotherapy containing regimens for metastatic disease
No prior exposure to cisplatin or ixabepilone
Expansion Phase Subjects: Advanced Non-small cell lung cancer
Inclusion Criteria:
Men and women age ≥ 18
Exclusion:
No prior chemotherapy-containing regimen for metastatic disease
No prior exposure to cisplatin or ixabepilone
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
The Cancer Institute Of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Local Institution
City
Lucca
ZIP/Postal Code
55100
Country
Italy
Facility Name
Local Institution
City
Meldola (Fc)
ZIP/Postal Code
47014
Country
Italy
Facility Name
Local Institution
City
Rimini
ZIP/Postal Code
47900
Country
Italy
Facility Name
Local Institution
City
Viterbo
ZIP/Postal Code
01100
Country
Italy
12. IPD Sharing Statement
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Phase I Combination Ixabepilone + Cisplatin
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