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

Carcinoma, Small Cell Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00537511
• Other study ID #: CC-4047-SCLC-002
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 1, 2008
• Est. completion date: December 1, 2010

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: December 1, 2010
• Est. primary completion date: November 1, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Small Cell

Intervention

Drug:
• Pomalidomide

• Cisplatin

• Etoposide

Locations

Country	Name	City	State
Canada	Juranvinski Cancer Center - Medical Oncology	Hamilton	Ontario
Canada	Mc Gill University - Department of Oncology - Clinical Research Program	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Ireland Cancer Center, Case Western Reserve University, Division of Hematology/Oncology	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Pennsylvania State University	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.)	Cycle 1 (21 days)
Secondary	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.	Cycles 1 - 6 (21-day cycles)
Secondary	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.	Cycles 1 -6 (21-day cycles)
Secondary	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.	From first Partial Response (PR) or Complete Response (CR) to disease progression (maximum of 19.4 weeks)
Secondary	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.	From enrollment through study termination (approximately 35 months)
Secondary	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.	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).
Secondary	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.	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).