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A Study of Pemetrexed and Bevacizumab for Participants With Advanced Non-Small Cell Cancer

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ClinicalTrials.gov Identifier: NCT01004250
Recruitment Status : Completed
First Posted : October 29, 2009
Results First Posted : December 25, 2013
Last Update Posted : May 21, 2014
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE October 28, 2009
First Posted Date  ICMJE October 29, 2009
Results First Submitted Date  ICMJE November 7, 2013
Results First Posted Date  ICMJE December 25, 2013
Last Update Posted Date May 21, 2014
Study Start Date  ICMJE October 2009
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2014)
Progression-Free Survival [ Time Frame: From enrollment to the first date of objectively determined Progressive Disease (PD) or death from any cause (every other cycle during study treatment and then every 6 weeks during follow-up period)(Baseline up to 36.1 Months) ]
Progression-Free Survival (PFS) is defined as the time from the date of study enrollment to the first date of objectively determined PD or death from any cause. PD is defined using Response Evaluation Criteria in Solid Tumours (RECIST) Guidelines (Version 1.0), as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last objective progression-free disease assessment. For participants who receive subsequent systemic anticancer therapy, PFS will be censored at the date of the last objective progression-free disease assessment prior to post-discontinuation systemic therapy.
Original Primary Outcome Measures  ICMJE
 (submitted: October 28, 2009)
Progression-Free Survival [ Time Frame: From enrollment to the first date of objectively determined Progressive disease or death from any cause (every other cycle during study treatment, and then every 6 weeks during follow-up period) ]
Change History Complete list of historical versions of study NCT01004250 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2014)
  • Overall Survival [ Time Frame: From enrollment to the date of death from any cause (every cycle during study treatment, every 6 weeks during follow-up period until PD, and then at least every 3 Months) (Baseline up to 36.3 Months) ]
    Overall Survival (OS) is defined as the time from the date of study enrollment to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS will be censored at the last contact date.
  • Percentage of Participants With Confirmed Complete Response or Partial Response During Study Treatment (Induction and Maintenance) [ Time Frame: From enrollment to objectively determined PD (assessment during study treatment completed at every other cycle till PD and at 30 day follow-up)(Baseline up to 104.1 Weeks) ]
    Overall Response Rate (ORR) is defined as the percentage of participants whose best response is complete response (CR) or partial response (PR) per RECIST Guidelines, Version 1.0. CR is disappearance of all tumor lesions. PR is either a) at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LDs, or b) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more nontarget lesions. In either case, no new lesions may have appeared.
  • Percentage of Participants With Confirmed Response Complete or Partial Response During the Induction Treatment Only [ Time Frame: From the time of study enrollment to the first date of objectively determined PD during the induction therapy (assessment during study treatment completed at every other cycle up to four cycles) (Baseline up to 4 cycles) ]
    CR and PR defined per RECIST Guidelines, Version 1.0. CR is disappearance of all tumor lesions. PR is either a) at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LDs, or b) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more nontarget lesions. In either case, no new lesions may have appeared.
  • Percentage of Participants With Confirmed Complete Response or Partial Response During the Maintenance Therapy Only [ Time Frame: From the start of the maintenance to the first date of objectively determined PD during the maintenance therapy (assessment during maintenance treatment completed at every other cycle till PD and at 30 day follow-up)(Cycle 5 up to 104.1 Weeks) ]
    CR and PR defined per RECIST Guidelines, Version 1.0. CR is disappearance of all tumor lesions. PR is either a) at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LDs, or b) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more nontarget lesions. In either case, no new lesions may have appeared.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2009)
  • Overall Survival [ Time Frame: From enrollment to the date of death from any cause (assessment completed during trial period at least every 3 months) ]
  • Proportion of patients with confirmed complete response or partial response during study treatment (Induction and Maintenance) [ Time Frame: From enrollment to objectively determined Progressive disease (assessment during study treatment completed at every other cycle till progressive disease) ]
  • Proportion of patients with confirmed response complete or partial response during the Induction treatment only [ Time Frame: From the time of study enrollment to the first date of objectively determined Progressive disease during the induction therapy (assessment during study treatment completed at every other cycle up to a maximum of four cycles) ]
  • Proportion of patients with confirmed complete response or partial response during the maintenance therapy only [ Time Frame: From the start of the maintenance to the first date of objectively determined Progressive disease during the maintenance therapy (assessment during maintenance treatment completed at every other cycle till progressive disease) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Pemetrexed and Bevacizumab for Participants With Advanced Non-Small Cell Cancer
Official Title  ICMJE A Single-Arm, Phase 2 Trial of Pemetrexed, Cisplatin,and Bevacizumab as Induction, Followed by Pemetrexed and Bevacizumab as Maintenance, in First-Line Treatment of Nonsquamous Advanced NSCLC
Brief Summary Participants with advanced non-small cell lung cancer (NSCLC) will receive a first-line treatment of Pemetrexed, Cisplatin and Bevacizumab as induction therapy followed by a maintenance treatment of Pemetrexed and Bevacizumab. Treatment will continue until disease progression or unacceptable toxicity occurs. The primary objective of this study is to measure how long this treatment could prevent the disease progression.
Detailed Description

The study will have 3 periods: a baseline period; a study treatment period, including both induction and maintenance treatment; and a follow-up period. Approximately 110 participants will be enrolled into the study, with the aim of having 100 evaluable participants. Eligible participants will first receive 4 cycles of induction chemotherapy with pemetrexed-cisplatin-bevacizumab. Participants who achieve a response or do not progress after completion of induction chemotherapy and have an adequate performance status will receive maintenance therapy with pemetrexed-bevacizumab. Treatment will continue until disease progression or unacceptable toxicity occurs. When treatment is discontinued, the participants health status will be monitored till death, loss to follow-up or data cut-off date.

Participants who continue to receive benefit from treatment at the time of data cut-off may receive continued access to pemetrexed and bevacizumab until disease progression, unacceptable toxicity, or any other reason at investigator or participants decision.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Pemetrexed
    500 milligram per square meter (mg/m²) given intravenously on Day 1 of each 21-day cycle for four cycles of Induction Therapy, and continued in Maintenance Therapy until progression or unacceptable toxicity.
    Other Names:
    • Alimta
    • LY231514
  • Drug: Cisplatin
    75 mg/m² given intravenously on Day 1 of 21-day cycle for a maximum of 4 cycles
  • Drug: Bevacizumab
    7.5 milligram per kilogram (mg/kg) given intravenously on Day 1 of 21-day cycle for four cycles of Induction Therapy, and continued in Maintenance Therapy until progression or unacceptable toxicity
Study Arms  ICMJE Experimental: Study Treatment
Interventions:
  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: Bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 7, 2013)
109
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2009)
110
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological or cytological diagnosis of nonsquamous Stage IIIB or Stage IV NSCLC that is not amenable to curative therapy
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • At least 1 unidimensionally measurable lesion meeting the Response Evaluation Criteria In Solid Tumors (RECIST) criteria
  • Adequate organ function, including the following:

    • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 10^9 per Liter (10^9/L), platelets ≥100 x 10^9/L, and hemoglobin ≥10 gram per deciliter (g/dL)
    • Hepatic: bilirubin ≤1.5 times the upper limit of normal (ULN); alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤3.0 x ULN (AP, AST, and ALT ≤5 x ULN is acceptable if liver has tumor involvement)
    • Renal: calculated creatinine clearance (CrCl) ≥45 milliliter per minute (mL/min) based on the original weight-based Cockcroft and Gault formula, and serum creatinine ≤1.5 x ULN
    • At the time of enrollment, if the urinalysis dipstick result is ≥2+ for protein, a 24-hour urine collection should be taken. In these cases, participants must have ≤1g protein/24 hours to be eligible for study participation
  • Participants must sign an Informed Consent Document (ICD)

Exclusion Criteria:

  • Have received prior systemic anticancer therapy for lung cancer (including adjuvant early-stage treatment for NSCLC)
  • Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV
  • Have a second primary malignancy that is clinically detectable at the time of consideration for study enrollment
  • Have known central nervous system (CNS) disease, other than stable, treated brain metastasis. Stable, treated brain metastasis is defined as metastasis having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and post-treatment brain imaging (Computed Tomography [CT] scan or magnetic resonance imaging [MRI])
  • Are receiving concurrent administration of any other antitumor therapy
  • Have a history of gastrointestinal fistula, perforation, or abscess, inflammatory bowel disease, or diverticulitis
  • Have had significant weight loss (that is, ≥10%) over the previous 6 weeks before study entry
  • Have a history of gross hemoptysis (bright red blood of ≥½ teaspoon per episode of coughing) <3 months prior to enrollment or history or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
  • Are taking or have recently taken (within 10 days of enrollment) full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes. Prophylactic use of anticoagulants is allowed; international normalized ratio (INR) should be <1.5 at study enrollment
  • Have a history of hypertension, unless hypertension is well controlled upon study entry (≤150/90 millimeter of mercury [mm Hg]) and the participant is on a stable regimen of antihypertensive therapy. Participants should not have any prior history of hypertensive crisis or hypertensive encephalopathy
  • Have had major surgery, open biopsy, or significant traumatic injury within 28 days prior to study enrollment, or anticipate the need for major surgical procedure during the course of the study
  • History of thrombotic disorders within the last 6 months prior to entry
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   Germany,   Italy,   Spain,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01004250
Other Study ID Numbers  ICMJE 13034
H3E-EW-S125 ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP