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A Study in Non Small Cell Lung Cancer

Primary Purpose

Non Small Cell Lung Cancer

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Pemetrexed

Cisplatin

LY2603618

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring solid tumors, Mesothelioma, Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Phase 1 portion:
- Participants with a cytologic or histologic diagnosis of nonsquamous NSCLC that is classified as Stage IV according to the 7th edition of the American Joint Committee on Cancer (AJCC) classification and for whom the combination of pemetrexed and cisplatin is deemed to be appropriate
- Participants with histologic or cytologic diagnosis of malignant mesothelioma that is unresectable
- Participants with histologic or cytologic diagnoses of advanced or metastatic solid tumors who are not candidates for any standard therapy and for whom the combination with pemetrexed and cisplatin is deemed to be appropriate
Phase 2 portion:
- Have a histological diagnosis of NSCLC other than predominantly squamous cell histology that is classified as Stage IV according to the 7th edition of the AJCC classification
- Eligible for a first line of palliative treatment with a platinum doublet
- Have archived or fresh tumor tissue (not cytology)
Phase 1 participants can have measurable or nonmeasurable disease. Phase 2 participants must have at least 1 measurable lesion according to Investigational New Drug (Response Evaluation Criteria in Solid Tumors [RECIST], v1.1) definitions. Tumor lesions located in a previously irradiated area can be considered measurable if they are new or if have shown unequivocal progression.
Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale
Have adequate hematologic, hepatic, and renal organ function
Prior radiation therapy for treatment of cancer is allowed to <25% of the bone marrow, and participants must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry
For women: Must be surgically sterile, postmenopausal, or compliant with a highly reliable contraceptive method (failure rate <1%) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period

Exclusion Criteria:

Have serious preexisting medical conditions or serious concomitant systemic disorders that would compromise the safety of the participant or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris or uncontrolled diabetes mellitus). Special attention should be paid to kidney and heart conditions that may be worsened with cisplatin treatment or hydration
Have central nervous system (CNS) metastases (unless the participant has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening computed tomography scan or magnetic resonance imaging before enrollment in the absence of a clinical suspicion of brain metastases is not required.
Have current active infection that would, in the opinion of the investigator, compromise the participant's ability to tolerate therapy
Have known allergy to pemetrexed, cisplatin, LY2603618, or any ingredient of pemetrexed, cisplatin, or LY2603618
Have clinically significant (by physical exam) third-space fluid collections; for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry
Participants taking non-steroidal anti-inflammatory drugs who cannot interrupt the treatment appropriately according to the guidelines
Have received a recent yellow-fever vaccination (within 28 days of enrollment) or are receiving concurrent yellow-fever vaccination
Phase 1 portion:
- Have received more than 2 previous lines of chemotherapy for the advanced/metastatic disease
- Have received more than 6 cycles of therapy containing an alkylating agent

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Phase 1: LY2603618 130 to 275 mg

Phase 2: Pemetrexed + Cisplatin + LY2603618

Phase 2: Pemetrexed + Cisplatin

Arm Description

Cycle 1-2 (21-day cycle): Day 1: pemetrexed 500 milligrams per meter square (mg/m^2) + cisplatin 75 mg/m^2 Day 2: LY2603618 at 130-275 milligrams (mg) After 2 cycles, participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.

Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 Day 2: LY2603618 dose from phase 1 portion of trial After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may continue on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion is met. Maintenance Therapy Experimental Arm (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1 After 25 Oct 2012: Day 1: pemetrexed 500 mg/m^2 If, as of 25 Oct 2012, participant was in maintenance therapy and randomized to the experimental arm, the participant is eligible to continue with pemetrexed (Day 1)/LY2603618 (Day 2) therapy if the investigator deems it is in the best interest of the participant and the participant consents.

Cycle 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m^2 + cisplatin 75 mg/m^2 After 4 cycles, participants may continue on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion is met. Maintenance Therapy Comparator Arm: Phase 2 (every 21 days): Day 1: pemetrexed 500 mg/m^2

Outcomes

Primary Outcome Measures

Phase 2: Progression-Free Survival Time

Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates.

Phase 1: Recommended Phase 2 Dose of LY2603618

The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after pemetrexed and cisplatin was based on the maximum tolerated dose (MTD) and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity [AUC(0-∞)] >21,000 nanogram*hour/milliliter [ng*h/mL] and maximum LY2603618 plasma concentration [Cmax] >2000 nanograms/milliliter [ng/mL]).

Secondary Outcome Measures

Phase 2: Overall Survival

Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates.

Phase 2: Overall Tumor Response Rate: Percentage of Participants Who Achieved a Confirmed Best Response of Completed Response (CR) or Partial Response (PR)

Overall response rate is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

Phase 2: Change in Tumor Size

Change in tumor size was based on tumor measurements collected according to RECIST, v1.1 guidelines. Tumor size is the sum of the tumor measurements (longest diameters) of target lesions at each tumor evaluation. Change in tumor size was defined as the change in log tumor size from baseline evaluation to the evaluation at the end of Cycle 2.

Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)

Cmax is reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point.

Phase 1: Pharmacokinetic: Cmax (Pemetrexed and Cisplatin)

Cmax for pemetrexed and total platinum (t-platinum) from cisplatin is reported. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug.

Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)

AUC from time zero to 24 hours (AUC[0-24]), AUC from time zero to the last time point with a measurable concentration (AUC[0-tlast]), and AUC from time zero to infinity (AUC[0-∞]) values are reported for each LY2603618 dose level on Cycle 1 /Day 2 and Cycle 2 /Day 2. The number of pharmacokinetic observations (n) used in the analysis is presented for each dose level and time point.

Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin)

AUC(0-tlast) and AUC(0-∞) values are reported for pemetrexed and t-platinum from cisplatin. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug.

Phase 2: Pharmacokinetic: Cmax (LY2603618)

Phase 2: Pharmacokinetic: AUC (LY2603618)

AUC (0-24), AUC(0-tlast), and AUC(0-∞) values are reported for LY2603618. The number of pharmacokinetic observations (n) used in the analysis is presented.

Phase 2: Change From Baseline to Long-term Follow up in Lung Cancer Symptom Scale (LCSS)

Health-related quality of life and participant symptoms were assessed using the LCSS (patient scale). However, improper implementation of questionnaires at the site level reduced the sponsor's ability to accurately evaluate the impacted data. Therefore, the LCSS data should be interpreted with caution. The LCSS is a 9-item questionnaire. Six questions are symptom-specific measures for lung cancer (appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items describe total symptomatic distress, activity status, and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-milliliter (mm) lines. Scores range from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was calculated as the mean of 6 symptom-specific questions from the LCSS. The total LCSS score was calculated as the mean of 9 questions from the LCSS.

Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers

Overall response rate is presented. Overall response rate is defined as the percentage of participants with a best response of CR or PR as classified by the investigators according to RECIST, v1.1 criteria. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

Phase 2: Proportion of Participants Receiving Maintenance Therapy

Phase 2: Clinical Benefit Rate: Percentage of Participant Who Achieved a Response of Stable Disease (SD), Partial Response (PR), or Complete Response (CR)

Clinical benefit rate is the best response CR, PR, or SD as classified by the investigators according to the RECIST, v1.1 guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

Full Information

NCT ID

NCT01139775

First Posted

June 1, 2010

Last Updated

May 16, 2018

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01139775

Brief Title

A Study in Non Small Cell Lung Cancer

Official Title

A Phase 1/Randomized Phase 2 Study to Evaluate LY2603618 in Combination With Pemetrexed and Cisplatin in Patients With Stage IV Non-small Cell Lung Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

February 2011 (undefined)

Primary Completion Date

May 2013 (Actual)

Study Completion Date

August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

LY2603618 is a selective inhibitor of the deoxyribonucleic acid (DNA) damage checkpoint kinase 1 (CHK1). It was being developed as a chemotherapeutic-enhancing agent in the treatment of cancer. Phase 1 studies have shown the feasibility of combining LY2603618 with either gemcitabine or pemetrexed. The objective of this study was to find the dose of LY2603618 that can be safely combined with standard doses of pemetrexed and cisplatin and to test if this triplet offered a significant improvement in progression-free survival (PFS) in participants with Stage IV nonsquamous non-small cell lung cancer (NSCLC) in the first-line of palliative treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non Small Cell Lung Cancer

Keywords

solid tumors, Mesothelioma, Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

76 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1: LY2603618 130 to 275 mg

Arm Type

Experimental

Arm Description

Arm Title

Phase 2: Pemetrexed + Cisplatin + LY2603618

Arm Type

Experimental

Arm Description

Arm Title

Phase 2: Pemetrexed + Cisplatin

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Intervention Description

Administered intravenously as a continuous 10-minute infusion

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Administered intravenously as a continuous 1-hour infusion

Intervention Type

Drug

Intervention Name(s)

LY2603618

Intervention Description

Administered intravenously as a continuous 1-hour infusion

Primary Outcome Measure Information:

Title

Phase 2: Progression-Free Survival Time

Description

Time Frame

Randomization up to first date of PD or death from any cause (up to 6 months after the last participant entered treatment)

Title

Phase 1: Recommended Phase 2 Dose of LY2603618

Description

Time Frame

Time of first dose to last dose

Secondary Outcome Measure Information:

Title

Phase 2: Overall Survival

Description

Time Frame

Randomization to the date of death from any cause through the time of study discontinuation (approximately 12 months after last participant was randomized)

Title

Phase 2: Overall Tumor Response Rate: Percentage of Participants Who Achieved a Confirmed Best Response of Completed Response (CR) or Partial Response (PR)

Description

Time Frame

Randomization until date of disease progression (up to 6 months after the last participant was randomized)

Title

Phase 2: Change in Tumor Size

Description

Time Frame

Baseline, end of Cycle 2

Title

Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)

Description

Time Frame

Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose

Title

Phase 1: Pharmacokinetic: Cmax (Pemetrexed and Cisplatin)

Description

Cmax for pemetrexed and total platinum (t-platinum) from cisplatin is reported. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug.

Time Frame

Pemetrexed: Cycle 1/Day 1 - immediately prior to end of pemetrexed infusion and 1, 2, 6 and 24 hours postdose. Cisplatin: Cycle 1/Day 1 - immediately prior to end of cisplatin infusion and 0.5, 1, 2, 6, 24, 72, 96, and 168 hours postdose.

Title

Phase 1: Pharmacokinetic: Area Under the Plasma Concentration Versus Time Curve (AUC) (LY2603618)

Description

Time Frame

Cycle 1/Day 2 - immediately prior to end of LY2603618 infusion and 1, 3, 6, 24, 48, 72, and 144 hours postdose; Cycle 2/Day 2 - predose, immediately prior to end of LY2603618 infusion, and 1, 3, 6, 24, 48, 72, and 144 hours postdose

Title

Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin)

Description

AUC(0-tlast) and AUC(0-∞) values are reported for pemetrexed and t-platinum from cisplatin. The number of pharmacokinetic observations (n) used in the analysis is presented for each drug.

Time Frame

Title

Phase 2: Pharmacokinetic: Cmax (LY2603618)

Time Frame

Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdose

Title

Phase 2: Pharmacokinetic: AUC (LY2603618)

Description

AUC (0-24), AUC(0-tlast), and AUC(0-∞) values are reported for LY2603618. The number of pharmacokinetic observations (n) used in the analysis is presented.

Time Frame

Cycle 1/Day 2 - predose, immediately prior to the end of the LY2603618 infusion, and 2-6, 24-48, and 72-96 hours postdose

Title

Phase 2: Change From Baseline to Long-term Follow up in Lung Cancer Symptom Scale (LCSS)

Description

Time Frame

Randomization to the end of study (approximately 12 months after the last participant entered treatment)

Title

Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers

Description

Time Frame

Baseline through end of Phase 1

Title

Phase 2: Proportion of Participants Receiving Maintenance Therapy

Time Frame

Cycle 5

Title

Phase 2: Clinical Benefit Rate: Percentage of Participant Who Achieved a Response of Stable Disease (SD), Partial Response (PR), or Complete Response (CR)

Description

Time Frame

Randomization until date of disease progression or death (up to 6 months after the last participant was randomized)

Other Pre-specified Outcome Measures:

Title

Deaths

Description

Deaths that occurred during the study are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Time Frame

Randomization through 12 months after the last participant was randomized

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Phase 1 portion: Participants with a cytologic or histologic diagnosis of nonsquamous NSCLC that is classified as Stage IV according to the 7th edition of the American Joint Committee on Cancer (AJCC) classification and for whom the combination of pemetrexed and cisplatin is deemed to be appropriate Participants with histologic or cytologic diagnosis of malignant mesothelioma that is unresectable Participants with histologic or cytologic diagnoses of advanced or metastatic solid tumors who are not candidates for any standard therapy and for whom the combination with pemetrexed and cisplatin is deemed to be appropriate Phase 2 portion: Have a histological diagnosis of NSCLC other than predominantly squamous cell histology that is classified as Stage IV according to the 7th edition of the AJCC classification Eligible for a first line of palliative treatment with a platinum doublet Have archived or fresh tumor tissue (not cytology) Phase 1 participants can have measurable or nonmeasurable disease. Phase 2 participants must have at least 1 measurable lesion according to Investigational New Drug (Response Evaluation Criteria in Solid Tumors [RECIST], v1.1) definitions. Tumor lesions located in a previously irradiated area can be considered measurable if they are new or if have shown unequivocal progression. Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale Have adequate hematologic, hepatic, and renal organ function Prior radiation therapy for treatment of cancer is allowed to <25% of the bone marrow, and participants must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry For women: Must be surgically sterile, postmenopausal, or compliant with a highly reliable contraceptive method (failure rate <1%) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period Exclusion Criteria: Have serious preexisting medical conditions or serious concomitant systemic disorders that would compromise the safety of the participant or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris or uncontrolled diabetes mellitus). Special attention should be paid to kidney and heart conditions that may be worsened with cisplatin treatment or hydration Have central nervous system (CNS) metastases (unless the participant has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening computed tomography scan or magnetic resonance imaging before enrollment in the absence of a clinical suspicion of brain metastases is not required. Have current active infection that would, in the opinion of the investigator, compromise the participant's ability to tolerate therapy Have known allergy to pemetrexed, cisplatin, LY2603618, or any ingredient of pemetrexed, cisplatin, or LY2603618 Have clinically significant (by physical exam) third-space fluid collections; for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry Participants taking non-steroidal anti-inflammatory drugs who cannot interrupt the treatment appropriately according to the guidelines Have received a recent yellow-fever vaccination (within 28 days of enrollment) or are receiving concurrent yellow-fever vaccination Phase 1 portion: Have received more than 2 previous lines of chemotherapy for the advanced/metastatic disease Have received more than 6 cycles of therapy containing an alkylating agent

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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.

City

Mannheim

State/Province

Baden-Wurttemberg

ZIP/Postal Code

68167

Country

Germany

Facility Name

City

Munster

State/Province

Nordhein-Westfalen

ZIP/Postal Code

48149

Country

Germany

Facility Name

City

Coswig

State/Province

Sachsen

ZIP/Postal Code

01640

Country

Germany

Facility Name

City

Berlin

ZIP/Postal Code

14165

Country

Germany

Facility Name

City

Frankfurt

ZIP/Postal Code

60596

Country

Germany

Facility Name

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

City

Heidelberg

ZIP/Postal Code

69126

Country

Germany

Facility Name

City

Homburg

ZIP/Postal Code

66421

Country

Germany

Facility Name

City

Immenhausen

ZIP/Postal Code

34376

Country

Germany

Facility Name

City

Lübeck

ZIP/Postal Code

23538

Country

Germany

Facility Name

City

Mainz

ZIP/Postal Code

D-55131

Country

Germany

Facility Name

City

Rheine

ZIP/Postal Code

48431

Country

Germany

Facility Name

City

Ulm

ZIP/Postal Code

89081

Country

Germany

Facility Name

City

Oviedo

State/Province

Asturias

ZIP/Postal Code

33006

Country

Spain

Facility Name

City

Mataro

State/Province

Barcelona

ZIP/Postal Code

08304

Country

Spain

Facility Name

City

Pozuelo de Alarcon

State/Province

Madrid

ZIP/Postal Code

28223

Country

Spain

Facility Name

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

City

Barcelona

ZIP/Postal Code

08908

Country

Spain

Facility Name

City

Girona

ZIP/Postal Code

17007

Country

Spain

Facility Name

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

City

Madrid

ZIP/Postal Code

28050

Country

Spain

Facility Name

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

28625637

Citation

Wehler T, Thomas M, Schumann C, Bosch-Barrera J, Vinolas Segarra N, Dickgreber NJ, Dalhoff K, Sebastian M, Corral Jaime J, Alonso M, Hynes SM, Lin J, Hurt K, Bence Lin A, Calvo E, Paz-Ares L. A randomized, phase 2 evaluation of the CHK1 inhibitor, LY2603618, administered in combination with pemetrexed and cisplatin in patients with advanced nonsquamous non-small cell lung cancer. Lung Cancer. 2017 Jun;108:212-216. doi: 10.1016/j.lungcan.2017.03.001. Epub 2017 Mar 6.

Results Reference

derived

PubMed Identifier

24942404

Citation

Calvo E, Chen VJ, Marshall M, Ohnmacht U, Hynes SM, Kumm E, Diaz HB, Barnard D, Merzoug FF, Huber L, Kays L, Iversen P, Calles A, Voss B, Lin AB, Dickgreber N, Wehler T, Sebastian M. Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer. Invest New Drugs. 2014 Oct;32(5):955-68. doi: 10.1007/s10637-014-0114-5. Epub 2014 Jun 20.

Results Reference

derived

Learn more about this trial

A Study in Non Small Cell Lung Cancer

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