Phase I Combination Ixabepilone + Cisplatin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00832117
First received: January 28, 2009
Last updated: March 24, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Non Small Cell Lung Cancer
Drug: Ixabepilone
Drug: Cisplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of Ixabepilone in Combination With Cisplatin in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Participants Experiencing Dose Limiting Toxicity (DLT) [ Time Frame: Within the first 21 days of first cycle ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Within the first 21 days of first cycle ] [ Designated as safety issue: Yes ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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 [ 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. ] [ Designated as safety issue: No ]
    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) [ 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.) ] [ Designated as safety issue: No ]
    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 [ 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. ] [ Designated as safety issue: Yes ]
    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 [ 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. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 30
Study Start Date: May 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Escalation and Expansion Drug: Ixabepilone
Escalation: Solution, intravenous (IV), 32-40 mg/m2, every 3 weeks, approximately 6 months
Other Name: 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 Name: IXEMPRA®
Drug: Cisplatin
Expansion: Solution, IV, 60-80 mg/m2, every 3 weeks, approximately 6 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00832117

Locations
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, New Jersey
The Cancer Institute Of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Italy
Local Institution
Lucca, Italy, 55100
Local Institution
Meldola (Fc), Italy, 47014
Local Institution
Rimini, Italy, 47900
Local Institution
Viterbo, Italy, 01100
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00832117     History of Changes
Other Study ID Numbers: CA163-177, 2008-004909-34
Study First Received: January 28, 2009
Results First Received: February 21, 2012
Last Updated: March 24, 2012
Health Authority: United States: Food and Drug Administration
Italy: Ministry of Health

Keywords provided by Bristol-Myers Squibb:
Lung Cancer (NSCLC)

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Cisplatin
Epothilones
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014