Phase I Combination Ixabepilone + Cisplatin

• Sponsor: R-Pharm (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00832117
• Collaborator: (none)
• Enrollment: 30
• Locations: 7
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.2

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: Ixabepilone; Drug: Cisplatin; Drug: Ixabepilone; Drug: Cisplatin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1 Study of Ixabepilone in Combination With Cisplatin in Subjects With Advanced Solid Tumors
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Escalation and Expansion

Drug: Ixabepilone; Escalation: Solution, intravenous (IV), 32-40 mg/m2, every 3 weeks, approximately 6 months; Other Names: IXEMPRA® ; Drug: Cisplatin; Escalation: Solution, IV, 60-100 mg/m2, every 3 weeks, approximately 6 months; Drug: Ixabepilone; Expansion: Solution, IV, 32 mg/m2, every 3 weeks, approximately 6 months; Other Names: IXEMPRA® ; Drug: Cisplatin; Expansion: Solution, IV, 60-80 mg/m2, every 3 weeks, approximately 6 months

Outcome Measures

Primary Outcome Measures

1. Participants Experiencing Dose Limiting Toxicity (DLT) [Within the first 21 days of first cycle]

   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.

2. Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of Cisplatin in Combination With Ixabepilone, 32 mg/m^2 [Within the first 21 days of first cycle]

   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

1. Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) [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.]

   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.

2. Percentage of Participants With Response [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.]

   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.

3. Duration of Response in Participants With Non-small Cell Lung Cancer (NSCLC) [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.)]

   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.

4. 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 [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.]

   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.

5. Number of Participants With Laboratory Abnormalities Per National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE)Version 3 Criteria [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.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
2	The Cancer Institute Of New Jersey	New Brunswick	New Jersey	United States	08901
3	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
4	Local Institution	Lucca		Italy	55100
5	Local Institution	Meldola (Fc)		Italy	47014
6	Local Institution	Rimini		Italy	47900
7	Local Institution	Viterbo		Italy	01100

Sponsors and Collaborators

• R-Pharm

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: R-Pharm
• ClinicalTrials.gov Identifier: NCT00832117
• Other Study ID Numbers: CA163-177; 2008-004909-34
• First Posted: Jan 29, 2009
• Last Update Posted: Oct 28, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by R-Pharm: Lung Cancer (NSCLC)
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Cisplatin; Epothilones

Study Results

Participant Flow

Pre-assignment Detail	A total of 30 participants were enrolled; 29 were treated (1 participant no longer met study criteria).

Arm/Group Title	All Enrolled Participants
Arm/Group Description	Participants received both ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 and ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle.
Period Title: Overall Study
STARTED	29
COMPLETED	17
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Ixa 32 mg/m^2+Cis 60 mg/m^2	32mg/m^2+Cis 80mg/m^2	Total
Arm/Group Description	6 participants with solid tumors (refractory to prior therapy) in the dose-escalation phase and 18 participants (with no prior chemotherapeutic treatment) with NSCLC in the dose-expansion phase received ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 administered intravenously on Day 1 of a 21 day cycle	5 participants in the dose-escalation phase with solid tumors (refractory to prior therapy) received ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle	Total of all reporting groups
Overall Participants	24	5	29
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	54	63
Age, Customized (participants) [Number]
< 65 years	12 50%	5 100%	17 58.6%
>= 65 years	12 50%	0 0%	12 41.4%
< 50 years	3 12.5%	2 40%	5 17.2%
>= 50 years	21 87.5%	3 60%	24 82.8%
Sex: Female, Male (Count of Participants)
Female	10 41.7%	2 40%	12 41.4%
Male	14 58.3%	3 60%	17 58.6%
Karnofsky Performance Status (participants) [Number]
80 - Activity with effort; some signs of disease	9 37.5%	2 40%	11 37.9%
90 - Normal activity; minor signs of disease	2 8.3%	1 20%	3 10.3%
100 - Normal no complaints; no evidence of disease	13 54.2%	2 40%	15 51.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

all treated participants

Arm/Group Title	Ixa 32 mg/m^2+Cis 60 mg/m^2	32mg/m^2+Cis 80mg/m^2
Arm/Group Description	6 participants with solid tumors (refractory to prior therapy) in the dose-escalation phase and 18 participants (with no prior chemotherapeutic treatment) with NSCLC in the dose-expansion phase received ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 administered intravenously on Day 1 of a 21 day cycle	5 participants in the dose-escalation phase with solid tumors (refractory to prior therapy) received ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle
Measure Participants	24	5
Number [participants]	0 0%	2 40%

2. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ixa 32 mg/m^2+Cis 60 mg/m^2	32mg/m^2+Cis 80mg/m^2
Arm/Group Description	6 participants with solid tumors (refractory to prior therapy) in the dose-escalation phase and 18 participants (with no prior chemotherapeutic treatment) with NSCLC in the dose-expansion phase received ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 administered intravenously on Day 1 of a 21 day cycle	5 participants in the dose-escalation phase with solid tumors (refractory to prior therapy) received ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle
Measure Participants	24	5
Complete Response	0 0%	0 0%
Partial Response	8 33.3%	0 0%
Stable Disease	10 41.7%	2 40%
Disease Progression	5 20.8%	2 40%
Not Assessed	1 4.2%	1 20%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All subjects who received at least 1 dose of either ixabepilone or carboplatin

Arm/Group Title	All Treated Participants
Arm/Group Description	All participants who received at least 1 dose of either ixabepilone or carboplatin
Measure Participants	29
Number [mg/m^2]	60

4. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed as the indication for NSCLC is no longer being pursued.

Arm/Group Title	Ixa 32 mg/m^2+Cis 60 mg/m^2	32mg/m^2+Cis 80mg/m^2
Arm/Group Description	6 participants with solid tumors (refractory to prior therapy) in the dose-escalation phase and 18 participants (with no prior chemotherapeutic treatment) with NSCLC in the dose-expansion phase received ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 administered intravenously on Day 1 of a 21 day cycle	5 participants in the dose-escalation phase with solid tumors (refractory to prior therapy) received ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle
Measure Participants	0	0

5. Secondary Outcome

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.)

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed as the indication for NSCLC is no longer being pursued.

Arm/Group Title	Ixa 32 mg/m^2+Cis 60 mg/m^2	32mg/m^2+Cis 80mg/m^2
Arm/Group Description	6 participants with solid tumors (refractory to prior therapy) in the dose-escalation phase and 18 participants (with no prior chemotherapeutic treatment) with NSCLC in the dose-expansion phase received ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 administered intravenously on Day 1 of a 21 day cycle	5 participants in the dose-escalation phase with solid tumors (refractory to prior therapy) received ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle
Measure Participants	0	0

6. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ixa 32 mg/m^2+Cis 60 mg/m^2	32mg/m^2+Cis 80mg/m^2
Arm/Group Description	6 participants with solid tumors (refractory to prior therapy) in the dose-escalation phase and 18 participants (with no prior chemotherapeutic treatment) with NSCLC in the dose-expansion phase received ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 administered intravenously on Day 1 of a 21 day cycle	5 participants in the dose-escalation phase with solid tumors (refractory to prior therapy) received ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle
Measure Participants	24	5
Death	4 16.7%	1 20%
SAEs	7 29.2%	2 40%
Drug-Related SAEs	4 16.7%	1 20%
AEs Leading to Discontinuation	2 8.3%	0 0%
Drug-Related AEs Leading to Discontinuation	1 4.2%	0 0%
Overall AEs	24 100%	5 100%
Grade 3/4 AEs	14 58.3%	3 60%
Drug-Related AEs	24 100%	5 100%
Grade 3/4 Drug-Related AEs	11 45.8%	3 60%

7. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Ixa 32 mg/m^2+Cis 60 mg/m^2	32mg/m^2+Cis 80mg/m^2
Arm/Group Description	6 participants with solid tumors (refractory to prior therapy) in the dose-escalation phase and 18 participants (with no prior chemotherapeutic treatment) with NSCLC in the dose-expansion phase received ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 administered intravenously on Day 1 of a 21 day cycle	5 participants in the dose-escalation phase with solid tumors (refractory to prior therapy) received ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle
Measure Participants	24	5
WBC, Grade 1-4	19 79.2%	5 100%
WBC, Grade 3-4	6 25%	3 60%
ANC, Grade 1-4	18 75%	5 100%
ANC, Grade 3-4	12 50%	4 80%
Platelet Count, Grade 1-4	9 37.5%	3 60%
Platelet Count, Grade 3-4	0 0%	1 20%
Hemoglobin, Grade 1-4	22 91.7%	5 100%
Hemoglobin, Grade 3-4	1 4.2%	0 0%

Adverse Events

Arm/Group Title	Ixa 32 mg/m2 + Cis 60 mg/m2		Ixa 32 mg/m2 +Cis 80 mg/m2
Arm/Group Description	6 participants with solid tumor (refractory to prior therapy) in the dose-escalation phase and 18 participants (with no prior chemotherapeutic treatment) for NSCLC in the dose-expansion phase received ixabepilone (ixa) 32 mg/m^2+ cisplatin (cis) 60 mg/m^2 administered intravenously on Day 1 of a 21 day cycle		5 participants in the dose-escalation phase with solid tumors (refractory to prior therapy) received ixa 32mg/m^2+cis 80mg/m^2, administered intravenously on Day 1 of a 21 day cycle
All Cause Mortality
	Ixa 32 mg/m2 + Cis 60 mg/m2		Ixa 32 mg/m2 +Cis 80 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ixa 32 mg/m2 + Cis 60 mg/m2		Ixa 32 mg/m2 +Cis 80 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/24 (29.2%)		2/5 (40%)
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA	1/24 (4.2%)		0/5 (0%)
Gastrointestinal disorders
NAUSEA	1/24 (4.2%)		0/5 (0%)
ABDOMINAL PAIN	0/24 (0%)		1/5 (20%)
VOMITING	2/24 (8.3%)		0/5 (0%)
Infections and infestations
BACTERAEMIA	1/24 (4.2%)		0/5 (0%)
BRONCHOPNEUMONIA	1/24 (4.2%)		0/5 (0%)
NEUTROPENIC SEPSIS	0/24 (0%)		1/5 (20%)
Nervous system disorders
CEREBRAL ISCHAEMIA	1/24 (4.2%)		0/5 (0%)
Psychiatric disorders
CONFUSIONAL STATE	1/24 (4.2%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS	1/24 (4.2%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Ixa 32 mg/m2 + Cis 60 mg/m2		Ixa 32 mg/m2 +Cis 80 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/24 (100%)		5/5 (100%)
Blood and lymphatic system disorders
NEUTROPENIA	8/24 (33.3%)		2/5 (40%)
ANAEMIA	4/24 (16.7%)		1/5 (20%)
THROMBOCYTOPENIA	1/24 (4.2%)		1/5 (20%)
Cardiac disorders
TACHYCARDIA	2/24 (8.3%)		1/5 (20%)
Ear and labyrinth disorders
EAR PRURITUS	0/24 (0%)		1/5 (20%)
EAR PAIN	0/24 (0%)		1/5 (20%)
EAR CANAL ERYTHEMA	0/24 (0%)		1/5 (20%)
Gastrointestinal disorders
NAUSEA	16/24 (66.7%)		3/5 (60%)
RECTAL HAEMORRHAGE	2/24 (8.3%)		0/5 (0%)
STOMATITIS	0/24 (0%)		1/5 (20%)
DIARRHOEA	6/24 (25%)		0/5 (0%)
CONSTIPATION	7/24 (29.2%)		4/5 (80%)
VOMITING	8/24 (33.3%)		1/5 (20%)
General disorders
MUCOSAL INFLAMMATION	3/24 (12.5%)		0/5 (0%)
PYREXIA	3/24 (12.5%)		1/5 (20%)
OEDEMA PERIPHERAL	3/24 (12.5%)		0/5 (0%)
OEDEMA	0/24 (0%)		1/5 (20%)
PAIN	3/24 (12.5%)		0/5 (0%)
ASTHENIA	5/24 (20.8%)		1/5 (20%)
FATIGUE	10/24 (41.7%)		4/5 (80%)
Hepatobiliary disorders
HYPERBILIRUBINAEMIA	0/24 (0%)		1/5 (20%)
Infections and infestations
RESPIRATORY MONILIASIS	0/24 (0%)		1/5 (20%)
RESPIRATORY TRACT INFECTION	0/24 (0%)		1/5 (20%)
HERPES VIRUS INFECTION	0/24 (0%)		1/5 (20%)
Investigations
TYMPANOMETRY ABNORMAL	0/24 (0%)		1/5 (20%)
ASPARTATE AMINOTRANSFERASE INCREASED	2/24 (8.3%)		1/5 (20%)
HAEMOGLOBIN DECREASED	0/24 (0%)		1/5 (20%)
PLATELET COUNT DECREASED	1/24 (4.2%)		1/5 (20%)
WHITE BLOOD CELL COUNT DECREASED	0/24 (0%)		2/5 (40%)
ALANINE AMINOTRANSFERASE INCREASED	1/24 (4.2%)		1/5 (20%)
WEIGHT DECREASED	2/24 (8.3%)		0/5 (0%)
INTERNATIONAL NORMALISED RATIO INCREASED	0/24 (0%)		1/5 (20%)
BLOOD ALKALINE PHOSPHATASE INCREASED	0/24 (0%)		1/5 (20%)
BLOOD CREATININE INCREASED	1/24 (4.2%)		1/5 (20%)
NEUTROPHIL COUNT DECREASED	1/24 (4.2%)		2/5 (40%)
Metabolism and nutrition disorders
HYPOCALCAEMIA	1/24 (4.2%)		1/5 (20%)
HYPOGLYCAEMIA	0/24 (0%)		1/5 (20%)
HYPERKALAEMIA	0/24 (0%)		1/5 (20%)
HYPOALBUMINAEMIA	0/24 (0%)		1/5 (20%)
HYPERMAGNESAEMIA	0/24 (0%)		1/5 (20%)
HYPOMAGNESAEMIA	3/24 (12.5%)		1/5 (20%)
HYPONATRAEMIA	0/24 (0%)		1/5 (20%)
DECREASED APPETITE	6/24 (25%)		0/5 (0%)
HYPERGLYCAEMIA	0/24 (0%)		1/5 (20%)
HYPOKALAEMIA	1/24 (4.2%)		2/5 (40%)
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY	3/24 (12.5%)		0/5 (0%)
MUSCULOSKELETAL PAIN	3/24 (12.5%)		0/5 (0%)
Nervous system disorders
DIZZINESS	2/24 (8.3%)		1/5 (20%)
NEUROPATHY PERIPHERAL	3/24 (12.5%)		0/5 (0%)
HEADACHE	2/24 (8.3%)		1/5 (20%)
PRESYNCOPE	0/24 (0%)		1/5 (20%)
DYSGEUSIA	5/24 (20.8%)		1/5 (20%)
NEUROTOXICITY	4/24 (16.7%)		0/5 (0%)
Psychiatric disorders
DEPRESSION	0/24 (0%)		2/5 (40%)
ANXIETY	1/24 (4.2%)		1/5 (20%)
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX	0/24 (0%)		1/5 (20%)
RESPIRATORY DISTRESS	0/24 (0%)		1/5 (20%)
COUGH	4/24 (16.7%)		2/5 (40%)
HAEMOPTYSIS	0/24 (0%)		1/5 (20%)
DYSPNOEA	2/24 (8.3%)		1/5 (20%)
DYSPNOEA EXERTIONAL	2/24 (8.3%)		0/5 (0%)
Skin and subcutaneous tissue disorders
DRY SKIN	0/24 (0%)		1/5 (20%)
DECUBITUS ULCER	0/24 (0%)		1/5 (20%)
ALOPECIA	8/24 (33.3%)		3/5 (60%)
RASH	3/24 (12.5%)		0/5 (0%)
Vascular disorders
FLUSHING	0/24 (0%)		1/5 (20%)
HYPOTENSION	0/24 (0%)		1/5 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.