Phase I Combination Ixabepilone + Cisplatin
- Registration Number
- NCT00832117
- Lead Sponsor
- R-Pharm
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- 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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Escalation and Expansion Cisplatin - Escalation and Expansion Ixabepilone -
- Primary Outcome Measures
Name Time Method 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.
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
Name Time Method 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.
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.
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.
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.
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.
Trial Locations
- Locations (4)
The Cancer Institute Of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Local Institution
🇮🇹Viterbo, Italy
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States