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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: Pemetrexed; Drug: Carboplatin	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 109 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: November 2009
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: June 2012

Arms and Interventions

Arm

Intervention/treatment

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

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.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

Japan

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.

Aichi, Japan, 460-0001

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.

Chiba, Japan, 277 8577

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Ehime, Japan, 790-0007

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Fukuoka, Japan, 812-8582

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Hokkaido, Japan, 062-0931

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Hyogo, Japan, 673-8558

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Kanagawa, Japan, 236-0051

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Kumamoto, Japan, 860-8556

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Miyagi, Japan, 980-8574

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Niigata, Japan, 951-8520

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.

Okayama, Japan, 700-8558

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Osaka, Japan, 589-8511

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Shizuoka, Japan, 411-8777

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Tochigi, Japan, 320-0834

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.

Tokyo, Japan, 113-8677

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.

Yamaguchi, Japan, 755-0241

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01020786 History of Changes
• Other Study ID Numbers: 12628; H3E-JE-JMII ( Other Identifier: Eli Lilly and Company )
• First Posted: November 26, 2009
• Results First Posted: March 16, 2012
• Last Update Posted: August 27, 2013
• Last Verified: June 2013

Keywords provided by Eli Lilly and Company:

Non-squamous

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carboplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors