A Study in Non-squamous Non Small Cell Lung Cancer in Asian Patients

• ClinicalTrials.gov Identifier: NCT01020786
• Recruitment Status: Completed
• First Posted: November 26, 2009
• Results First Posted: March 16, 2012
• Last Update Posted: August 27, 2013
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: November 24, 2009
• First Posted Date: November 26, 2009
• Results First Submitted Date: January 12, 2012
• Results First Posted Date: March 16, 2012
• Last Update Posted Date: August 27, 2013
• Study Start Date: November 2009
• Actual Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2012)

Progression Free Survival (PFS) During the Induction and Maintenance Therapy Periods [ Time Frame: Enrollment to the date of progressive disease (PD) or the date of death from any cause (up to 18 months) ]

PFS defined as time from enrollment date to first date of objective progression of disease or of death from any cause. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments. Participants receiving any subsequent systemic anticancer therapy before objective progression or death were censored at date of last objective progression-free disease assessment before starting subsequent systemic anticancer therapy.

• Original Primary Outcome Measures (submitted: November 24, 2009): Progression Free Survival (induction + maintenance therapy) [ Time Frame: Enrollment to the date of progressive disease or the date of death from any cause ]

Current Secondary Outcome Measures (submitted: June 19, 2013)

• Overall Survival (OS) During the Induction and Maintenance Therapy Periods [ Time Frame: Enrollment to the date of death from any cause (up to 30.8 months) ]
  OS was defined as the time from the enrollment date to the date of death from any cause. For participants who were alive, OS was censored at the last contact.
• Percentage of Participants Who Achieve a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Induction and Maintenance Therapy Periods [ Time Frame: Enrollment to date of progressive disease (up to 18 months) ]
  Calculated as the percentage of participants who achieved a confirmed CR, PR, or SD. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments. CR = disappearance of all target lesions. PR = 30% decrease in the sum of the longest diameter of target lesions. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions. SD = small changes that do not meet above criteria.
• Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) During the Induction and Maintenance Therapy Periods [ Time Frame: Enrollment to date of progressive disease (up to 18 months) ]
  Calculated as the percentage of participants who achieved a confirmed CR or PR. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments. CR = disappearance of all target lesions. PR = 30% decrease in the sum of the longest diameter of target lesions. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable Disease (SD) = small changes that do not meet above criteria.
• Progression Free Survival (PFS) During the Maintenance Therapy Period [ Time Frame: From the start of maintenance therapy in Cycle 5 (21-day cycle) until the date of measured progressive disease (PD) or death from any cause (up to 24.4 months) ]
  Measured from the date of the first dose of the maintenance therapy. Calculated by subtracting induction therapy period from PFS. Tumor response assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0; define when cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments. Participants receiving any subsequent systemic anticancer therapy before objective progression or death were censored at date of last objective progression-free disease assessment before starting subsequent systemic anticancer therapy.
• Overall Survival (OS) During the Maintenance Therapy Period [ Time Frame: From the start of maintenance therapy in Cycle 5 (21-day cycle) until the date of measured progressive disease (PD) or death from any cause (up to 26.3 months) ]
  OS was defined as the duration from the date of the first dose of the maintenance therapy to the date of death from any cause and was calculated by subtracting the induction therapy period from OS. Participants receiving any subsequent systemic anticancer therapy before objective progression or death were censored at date of last objective progression-free disease assessment before starting subsequent systemic anticancer therapy. For participants who were alive, OS was censored at the last contact.
• Percentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Maintenance Therapy Period [ Time Frame: From the start of maintenance therapy in Cycle 5 (21-day cycle) until the date of measured progressive disease (PD) or death from any cause (up to 18 months) ]
  Percentage of participants who achieved confirmed CR (disappearance of all target lesions), PR (30% decrease in sum of longest diameter of target lesions), or SD (small changes that do not meet above criteria). Response derived from target lesion assessments performed before maintenance therapy (as baseline), during maintenance therapy (as post-baseline), and non-target lesion assessments performed during maintenance therapy according to RECIST guideline version 1.0, defines when cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments.
• Percentage of Participants Who Observe a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Induction Therapy Period [ Time Frame: Enrollment to the date of PD, or end of induction period up to Cycle 4 (21-day cycle) ]
  Calculated as the percentage of participants who achieved a CR, PR, or SD (confirmed or not). Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments. CR = disappearance of all target lesions. PR = 30% decrease in the sum of the longest diameter of target lesions. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions. SD = small changes that do not meet above criteria.
• Percentage of Participants Who Achieve a Complete Response (CR) or a Partial Response (PR) During the Induction Therapy Period [ Time Frame: Enrollment to date of PD, or end of induction period up to Cycle 4 (21-day cycle) ]
  Calculated as percentage of participants who achieved a CR or PR (confirmed or not). Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments. CR = disappearance of all target lesions. PR = 30% decrease in sum of the longest diameter of target lesions. Progressive Disease (PD) = 20% increase in the sum of longest diameter of target lesions. Stable Disease (SD) = small changes that do not meet above criteria.

Original Secondary Outcome Measures (submitted: November 24, 2009)

• Overall Survival (induction + maintenance therapy) [ Time Frame: Enrollment to the date of death from any cause ]
• Proportion of patients who achieve a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (induction + maintenance therapy) [ Time Frame: Enrollment to date of progressive disease ]
• Proportion of patients who achieve a CR or PR (induction + maintenance therapy) [ Time Frame: Enrollment to date of progressive disease ]
• Progression Free Survival (maintenance therapy) [ Time Frame: From the start of maintenance therapy in cycle 5 until the date of measured progressive disease or death from any cause ]
• Overall Survival (maintenance therapy) [ Time Frame: From the start of maintenance therapy in cycle 5 until the date of measured progressive disease or death from any cause ]
• Proportion of patients who achieve a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (maintenance therapy) [ Time Frame: From the start of maintenance therapy in cycle 5 until the date of measured progressive disease or death from any cause ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study in Non-squamous Non Small Cell Lung Cancer in Asian Patients
• Official Title: Post-marketing Clinical Trial of Induction Chemotherapy of Pemetrexed Plus Carboplatin Followed by Pemetrexed Maintenance Therapy for Advanced Nonsquamous Non-small Cell Lung Cancer
• Brief Summary: To investigate efficacy and safety of the combination with pemetrexed plus carboplatin, followed by pemetrexed in patients with advanced nonsquamous Non Small Cell Lung Cancer (NSCLC) who receive at least one dose of the induction therapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer

Intervention

• Drug: Pemetrexed

  Induction Therapy: 500 milligrams per square meter (mg/m^2) given intravenously (IV) on Day 1 of every 21-day cycle for 4 cycles.

  Maintenance Therapy: 500 mg/m^2 given IV on Day 1 of every 21-day cycle until disease progression or unacceptable toxicity.

  Other Names:

  • Alimta
  • LY231514
• Drug: Carboplatin
  Dosage equal to area under the curve (AUC)6 milligrams per milliliter per minute (mg/mL/min) for participant, given IV on Day 1 of every 21-day cycle for 4 cycles.

Study Arms

Experimental: Pemetrexed + Carboplatin

After four 21-day cycles of Pemetrexed plus Carboplatin treatment, Pemetrexed monotherapy is continued until study discontinuation.

Interventions:

• Drug: Pemetrexed
• Drug: Carboplatin

• Publications *: Okamoto I, Aoe K, Kato T, Hosomi Y, Yokoyama A, Imamura F, Kiura K, Hirashima T, Nishio M, Nogami N, Okamoto H, Saka H, Yamamoto N, Yoshizuka N, Sekiguchi R, Kiyosawa K, Nakagawa K, Tamura T. Pemetrexed and carboplatin followed by pemetrexed maintenance therapy in chemo-naïve patients with advanced nonsquamous non-small-cell lung cancer. Invest New Drugs. 2013 Oct;31(5):1275-82. doi: 10.1007/s10637-013-9941-z. Epub 2013 Mar 10. Erratum in: Invest New Drugs. 2013 Oct;31(5):1395-6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 17, 2012): 109
• Original Estimated Enrollment (submitted: November 24, 2009): 100
• Actual Study Completion Date: June 2012
• Actual Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Non-squamous cell Non Small Cell Lung Cancer (NSCLC) disease
• Clinical stage IIIB/IV or recurrent disease after surgery
• No prior systemic chemotherapy, immunotherapy, targeted therapy or biological therapy, including adjuvant therapy
• Prior radiation therapy is allowed to less than 25% of the bone marrow
• Measurable disease as defined by response evaluation criteria in solid tumors (RECIST)
• The Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate organ function
• Estimated life expectancy of at least 12 weeks

Exclusion Criteria:

• Clinically significant third-space fluid collections
• Central nervous system disease other than stable and treated brain metastasis
• More than 3 weeks interval between the surgery and enrollment request date
• Unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), for a 5 days period
• Unable or unwilling to take folic acid or vitamin B12 supplementation
• Unable to take corticosteroids.
• Serious concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol
• Currently have and historically had interstitial pneumonitis (interstitial pneumonia) or pulmonary fibrosis manifested as opacity on Chest x-ray or Computed tomography (CT)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT01020786
• Other Study ID Numbers: 12628; H3E-JE-JMII ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: June 2013