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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01004250
First received: October 28, 2009
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Pemetrexed
Drug: Cisplatin
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 109
Study Start Date: October 2009
Study Completion Date: December 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Treatment 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004250

Locations
Denmark
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Copenhagen, Denmark, 2200
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Herlev, Denmark, 2730
Germany
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Coswig, Germany, 01640
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Frankfurt, Germany, 60431
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Hamburg, Germany, 22087
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Hamm, Germany, 59071
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Hannover, Germany, 30625
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Magdeburg, Germany, D-39120
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Mannheim, Germany, 68167
Italy
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Lecce, Italy, 73100
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Padova, Italy, 35128
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Rome, Italy, 00144
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Rozzano, Italy, 20089
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Trento, Italy, 38100
Spain
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Jaen, Spain, 23007
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Madrid, Spain, 28046
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Pozuelo De Alarcon, Spain, 28223
Sweden
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Malmo, Sweden, 205 02
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Solna, Sweden, 17176
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01004250     History of Changes
Other Study ID Numbers: 13034, H3E-EW-S125
Study First Received: October 28, 2009
Results First Received: November 7, 2013
Last Updated: April 23, 2014
Health Authority: Denmark: Danish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Bevacizumab
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on October 19, 2014