Phase I Combination Ixabepilone + Cisplatin

Phase 1 Study of Ixabepilone in Combination With Cisplatin in Subjects With Advanced Solid Tumors

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

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Ixabepilone; Drug: Cisplatin; Drug: Ixabepilone; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Lucca, Italy, 55100
    • Local Institution
  • Meldola (Fc), Italy, 47014
    • Local Institution
  • Rimini, Italy, 47900
    • Local Institution
  • Viterbo, Italy, 01100
    • Local Institution
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • The Cancer Institute of New Jersey
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within the first 21 days of first cycle
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.	Within the first 21 days of first cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.
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.	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.
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.	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.)
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.	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.
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.	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.

Collaborators and Investigators

• Sponsor: R-Pharm

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: January 28, 2009
• First Submitted That Met QC Criteria: January 28, 2009
• First Posted (Estimate): January 29, 2009

Study Record Updates

• Last Update Posted (Actual): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Lung Cancer (NSCLC)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Cisplatin; Epothilones
• Other Study ID Numbers: CA163-177; 2008-004909-34