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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01004250
• Other study ID #: 13034
• Secondary ID: H3E-EW-S125
• Status: Completed
• Phase: Phase 2
• First received: October 28, 2009
• Last updated: April 23, 2014
• Start date: October 2009
• Est. completion date: December 2013

Study information

• Verified date: April 2014
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthSpain: Spanish Agency of MedicinesSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: December 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Small Cell Lung Cancer

Intervention

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.
• Cisplatin
75 mg/m² given intravenously on Day 1 of 21-day cycle for a maximum of 4 cycles
• 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

Locations

Country	Name	City	State
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	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.	Herlev
Germany	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.	Coswig
Germany	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.	Frankfurt
Germany	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.	Hamburg
Germany	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.	Hamm
Germany	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.	Hannover
Germany	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.	Magdeburg
Germany	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.	Mannheim
Italy	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.	Lecce
Italy	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.	Padova
Italy	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.	Rome
Italy	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.	Rozzano
Italy	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.	Trento
Spain	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.	Jaen
Spain	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.	Madrid
Spain	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.	Pozuelo De Alarcon
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	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

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Denmark,  Germany,  Italy,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival	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.	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)	No
Secondary	Overall Survival	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.	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)	No
Secondary	Percentage of Participants With Confirmed Complete Response or Partial Response During Study Treatment (Induction and Maintenance)	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.	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)	No
Secondary	Percentage of Participants With Confirmed Response Complete or Partial Response During the Induction Treatment Only	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.	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)	No
Secondary	Percentage of Participants With Confirmed Complete Response or Partial Response During the Maintenance Therapy Only	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.	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)	No