Back to resultsA Phase I/II Study to Determine the Maximum Tolerated Dose (MTD) and Safety of CC-4047 (Pomalidomide) Administered in Conjunction With Cisplatin and Etoposide
Primary Purpose
Carcinoma, Small Cell
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Pomalidomide
Cisplatin
Etoposide
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Small Cell
Eligibility Criteria
Inclusion Criteria:
- signature of informed consent
- Age >= 18
- histologically or cytologically confirmed small cell lung cancer (SCLC)
- extensive stage SCLC
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
- brain metastases that are asymptomatic and do not require steroid control
- females of child bearing potential must use two forms of birth control
Exclusion Criteria:
- pregnant or lactating females
- prior use of cytotoxic chemotherapy
- surgery within 14 days of study
- radiation within 14 days of study
- prior therapy with CC-4047 (pomalidomide), lenalidomide or thalidomide
- concurrent use or anticipated use of anti-cancer agents
- absolute neutrophil count (ANC) < 1500/mm^3
- platelets < 100 x 10^3/µL
- serum creatinine >2.5 mg/dL
- serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 3.0 x upper limit of normal (ULN)
- serum total bilirubin > 1.8 mg/dL
- uncontrolled hypercalcemia
- creatinine clearance <50 mL/min
- uncontrolled hypertension
- neuropathy >= grade 2
- body mass index (BMI) >= 40
- any other active invasive malignancy requiring treatment
- known chronic infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
- inability or unwillingness to comply with birth control requirements
Sites / Locations
- Ireland Cancer Center, Case Western Reserve University, Division of Hematology/Oncology
- Pennsylvania State University
- University of Texas Southwestern Medical Center
- Juranvinski Cancer Center - Medical Oncology
- Princess Margaret Hospital
- Mc Gill University - Department of Oncology - Clinical Research Program
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose-finding arm: Pomalidomide + Cisplatin + Etoposide
Arm Description
Oral pomalidomide 1 mg - 5 mg daily (QD) for 14 consecutive days of a 21-day cycle, in combination with intravenous (IV) cisplatin 25 mg/m^2 and IV etoposide 100 mg/m^2 on Days 1, 2 and 3 of each cycle during the dose-finding phase (Treatment and Extension Periods; 6 cycles in total). Dose escalation followed a standard phase 1 3+3 design. Participants continuing took only their pomalidomide dose (monotherapy) for an additional 3-week Recovery Period (14 days of consecutive dosing followed by 7 days of no study medication). Participants continuing took oral pomalidomide 5 mg QD as monotherapy for 14 consecutive days of each 21-day cycle until disease progression in the Maintenance Phase.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle of treatment. The MTD Phase included the Treatment period (Cycle 1: Identification of the MTD) and the Extension period (Cycles 2 to 6: Confirmation of Safety of the MTD). (See Secondary Outcome Measure 2 for data on DLTs.)
Secondary Outcome Measures
Number of Participants With Dose Limiting Toxicities (DLTs) During the MTD Phase
For the purposes of determining the MTD (see Primary Outcome Measure), a DLT was defined as any 1 or more of the following: inability to deliver all 3 doses of cisplatin and etoposide due to toxicity; inability to deliver 14 consecutive days of daily pomalidomide dosing because the participant did not tolerate the medication due to any of the following: ≥ grade 3 non-hematological toxicity (excluding alopecia) occurring before Day 14 of pomalidomide dosing; febrile neutropenia (absolute neutrophil count [ANC] <1,000/µL and fever >101ºF, core temperature); grade 4 neutropenia of ≥7 days duration with onset on or before Day 14 of pomalidomide dosing; platelet count <25,000/µL occurring before Day 14 of pomalidomide dosing. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 4.0, grades: 1=mild, 2=moderate, 3=severe, 4=life threatening, 5=death.
Tumor Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST)
Investigator's best assessment of response based on RECIST criteria during the MTD phase. For target lesions: Complete Response (CR)=Disappearance of all target lesions; Partial Response (PR)=≥30% decrease in sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD; Progressed Disease (PD)=≥20% increase in sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or the appearance of ≥1 new lesions; Stable Disease (SD)=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since treatment started. For non-target lesions: CR= Disappearance of all non-target lesions and normalization of tumor marker level; Incomplete Response/SD=Persistence of ≥1 non-target lesions and/or maintenance of tumor marker level above normal limits; PD=Appearance of ≥1 new lesions; unequivocal progression of existing non-target lesions.
Duration of Response
Duration of Response was calculated from first Partial Response (PR) or Complete Response (CR) to disease progression. Duration of response was censored at the last date that the participant was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had been removed from the treatment phase prior to documentation of progression.
Overall Survival
Overall Survival was defined as time (in weeks) from enrollment to death. The median is based on Kaplan-Meier estimate, with 95% confidence intervals about the median overall survival. Overall survival was censored at the last time participant was known to be alive for those who were alive at time of analysis.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the MTD (Combination Treatment) Phase
Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 4.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Recovery Period or Maintenance (Monotherapy) Phase
Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. TEAE = any AE occurring or worsening on or after the first treatment with any study drug. 'Related' = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 4.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00537511
Brief Title
A Phase I/II Study to Determine the Maximum Tolerated Dose (MTD) and Safety of CC-4047 (Pomalidomide) Administered in Conjunction With Cisplatin and Etoposide
Official Title
A Multicenter, Phase I/IIA, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose and To Evaluate the Safety Profile of CC-4047 Administered in Combination With Cisplatin and Etoposide in Patients With Extensive Disease Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated for administrative reasons.
Study Start Date
February 1, 2008 (Actual)
Primary Completion Date
November 1, 2010 (Actual)
Study Completion Date
December 1, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the maximum tolerated dose and safety of CC-4047 (pomalidomide) given in combination with cisplatin and etoposide in patients with extensive disease small cell lung cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Small Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose-finding arm: Pomalidomide + Cisplatin + Etoposide
Arm Type
Experimental
Arm Description
Oral pomalidomide 1 mg - 5 mg daily (QD) for 14 consecutive days of a 21-day cycle, in combination with intravenous (IV) cisplatin 25 mg/m^2 and IV etoposide 100 mg/m^2 on Days 1, 2 and 3 of each cycle during the dose-finding phase (Treatment and Extension Periods; 6 cycles in total). Dose escalation followed a standard phase 1 3+3 design. Participants continuing took only their pomalidomide dose (monotherapy) for an additional 3-week Recovery Period (14 days of consecutive dosing followed by 7 days of no study medication). Participants continuing took oral pomalidomide 5 mg QD as monotherapy for 14 consecutive days of each 21-day cycle until disease progression in the Maintenance Phase.
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Other Intervention Name(s)
CC-4047, Pomalyst
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisplatinum, CDDP, Platin
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Etoposide phosphate, VP-16, Etopophos
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle of treatment. The MTD Phase included the Treatment period (Cycle 1: Identification of the MTD) and the Extension period (Cycles 2 to 6: Confirmation of Safety of the MTD). (See Secondary Outcome Measure 2 for data on DLTs.)
Time Frame
Cycle 1 (21 days)
Secondary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLTs) During the MTD Phase
Description
For the purposes of determining the MTD (see Primary Outcome Measure), a DLT was defined as any 1 or more of the following: inability to deliver all 3 doses of cisplatin and etoposide due to toxicity; inability to deliver 14 consecutive days of daily pomalidomide dosing because the participant did not tolerate the medication due to any of the following: ≥ grade 3 non-hematological toxicity (excluding alopecia) occurring before Day 14 of pomalidomide dosing; febrile neutropenia (absolute neutrophil count [ANC] <1,000/µL and fever >101ºF, core temperature); grade 4 neutropenia of ≥7 days duration with onset on or before Day 14 of pomalidomide dosing; platelet count <25,000/µL occurring before Day 14 of pomalidomide dosing. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 4.0, grades: 1=mild, 2=moderate, 3=severe, 4=life threatening, 5=death.
Time Frame
Cycles 1 - 6 (21-day cycles)
Title
Tumor Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST)
Description
Investigator's best assessment of response based on RECIST criteria during the MTD phase. For target lesions: Complete Response (CR)=Disappearance of all target lesions; Partial Response (PR)=≥30% decrease in sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD; Progressed Disease (PD)=≥20% increase in sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or the appearance of ≥1 new lesions; Stable Disease (SD)=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since treatment started. For non-target lesions: CR= Disappearance of all non-target lesions and normalization of tumor marker level; Incomplete Response/SD=Persistence of ≥1 non-target lesions and/or maintenance of tumor marker level above normal limits; PD=Appearance of ≥1 new lesions; unequivocal progression of existing non-target lesions.
Time Frame
Cycles 1 -6 (21-day cycles)
Title
Duration of Response
Description
Duration of Response was calculated from first Partial Response (PR) or Complete Response (CR) to disease progression. Duration of response was censored at the last date that the participant was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had been removed from the treatment phase prior to documentation of progression.
Time Frame
From first Partial Response (PR) or Complete Response (CR) to disease progression (maximum of 19.4 weeks)
Title
Overall Survival
Description
Overall Survival was defined as time (in weeks) from enrollment to death. The median is based on Kaplan-Meier estimate, with 95% confidence intervals about the median overall survival. Overall survival was censored at the last time participant was known to be alive for those who were alive at time of analysis.
Time Frame
From enrollment through study termination (approximately 35 months)
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the MTD (Combination Treatment) Phase
Description
Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 4.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.
Time Frame
Cycles 1-6 (21-day cycles). Median (full range) duration of exposure (in weeks) to pomalidomide (MTD Phase): 1 mg, 17.9 (1.0, 20.3); 3 mg, 17.0 (16.9, 22.0); 4 mg, 14.0 (0.7, 22.0); 5 mg, 13.0 (2.0, 22.1). Cisplatin and etoposide: 15.3 (0.4, 20.6).
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Recovery Period or Maintenance (Monotherapy) Phase
Description
Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. TEAE = any AE occurring or worsening on or after the first treatment with any study drug. 'Related' = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 4.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.
Time Frame
Cycle 7 to discontinuation (21-day cycles). Median (full range) duration of exposure (in weeks) to pomalidomide during Maintenance Phase was 5.0 (1.1, 36.0).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
signature of informed consent
Age >= 18
histologically or cytologically confirmed small cell lung cancer (SCLC)
extensive stage SCLC
Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
brain metastases that are asymptomatic and do not require steroid control
females of child bearing potential must use two forms of birth control
Exclusion Criteria:
pregnant or lactating females
prior use of cytotoxic chemotherapy
surgery within 14 days of study
radiation within 14 days of study
prior therapy with CC-4047 (pomalidomide), lenalidomide or thalidomide
concurrent use or anticipated use of anti-cancer agents
absolute neutrophil count (ANC) < 1500/mm^3
platelets < 100 x 10^3/µL
serum creatinine >2.5 mg/dL
serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 3.0 x upper limit of normal (ULN)
serum total bilirubin > 1.8 mg/dL
uncontrolled hypercalcemia
creatinine clearance <50 mL/min
uncontrolled hypertension
neuropathy >= grade 2
body mass index (BMI) >= 40
any other active invasive malignancy requiring treatment
known chronic infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
inability or unwillingness to comply with birth control requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ulf Jungnelius, MD
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Ireland Cancer Center, Case Western Reserve University, Division of Hematology/Oncology
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Pennsylvania State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Juranvinski Cancer Center - Medical Oncology
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Mc Gill University - Department of Oncology - Clinical Research Program
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
23370364
Citation
Ellis PM, Jungnelius U, Zhang J, Fandi A, Beck R, Shepherd FA. A phase I study of pomalidomide (CC-4047) in combination with cisplatin and etoposide in patients with extensive-stage small-cell lung cancer. J Thorac Oncol. 2013 Apr;8(4):423-8. doi: 10.1097/JTO.0b013e318282707b. Erratum In: J Thorac Oncol. 2019 Aug;14(8):1484.
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A Phase I/II Study to Determine the Maximum Tolerated Dose (MTD) and Safety of CC-4047 (Pomalidomide) Administered in Conjunction With Cisplatin and Etoposide
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