A Study in Non Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01139775
First received: June 1, 2010
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

LY2603618 is a potent and selective inhibitor of the deoxyribonucleic acid (DNA) damage checkpoint kinase 1 (Chk1). It is being developed as a chemotherapeutic-enhancing agent in the treatment of cancer. Ongoing Phase 1 studies have shown the feasibility of combining LY2603618 with either gemcitabine or pemetrexed. The objective of this study is to find the dose of LY2603618 that can be safely combined with standard doses of pemetrexed and cisplatin and to test if this triplet offers a significant improvement in progression-free survival in participants with Stage IV nonsquamous non-small cell lung cancer (NSCLC) in the first-line of palliative treatment.


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: Pemetrexed
Drug: Cisplatin
Drug: LY2603618
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Phase 2: Progression Free Survival Time [ Time Frame: Randomization up to First Date of Progressive Disease or Death from Any Cause (up to 6 Months after last participant entered treatment) ] [ Designated as safety issue: No ]
  • Phase 1: Recommended Phase 2 Dose of LY2603618 [ Time Frame: Time of First Dose to Last Dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase 2: Overall Survival [ Time Frame: Randomization to the Date of Death from Any Cause (up to 12 Months after last participant entered treatment) ] [ Designated as safety issue: No ]
  • Phase 2: Overall Tumor Response Rate: Percentage of Participants who Achieved a Confirmed Best Response of Completed Response (CR) or Partial Response (PR) [ Time Frame: Randomization until Date of Disease Progression (PD) (up to 12 Months after last participant randomized for study) ] [ Designated as safety issue: No ]
  • Phase 2: Change in Tumor Size [ Time Frame: Baseline, End of Cycle 2 ] [ Designated as safety issue: No ]
  • Phase 1: Pharmacokinetic: Maximum Concentration (Cmax) (Pemetrexed, Cisplatin and LY2603618) [ Time Frame: Cycle 1 and Cycle 2 of Phase 1 ] [ Designated as safety issue: No ]
  • Phase 1: Pharmacokinetic: Area Under the Curve (AUC) (Pemetrexed,Cisplatin and LY2603618) [ Time Frame: Cycle 1 and Cycle 2 of Phase 1 ] [ Designated as safety issue: No ]
  • Phase 2: Pharmacokinetic: Maximum Concentration (Cmax) (LY2603618) [ Time Frame: Cycle 1 of Phase 2 ] [ Designated as safety issue: No ]
  • Phase2: Pharmacokinetic: Area Under the Curve (AUC) (LY2603618) [ Time Frame: Cycle 1 of Phase 2 ] [ Designated as safety issue: No ]
  • Phase 2: Change from Baseline to Long Term Follow-Up in Lung Cancer Symptom Scale (LCSS) [ Time Frame: Baseline, Long Term Follow-Up (up to 15 Month after last participant entered treatment) ] [ Designated as safety issue: No ]
  • Phase 1: Document any antitumor activity per radiological scans and/or tumor markers [ Time Frame: During every cycle of Phase 1 (from baseline through end of Phase 1; estimated to be up to 12 Months) ] [ Designated as safety issue: No ]
  • Phase 2: Proportion of Participants Receiving Maintenance Therapy [ Time Frame: Cycle 5 ] [ Designated as safety issue: No ]
  • Phase 2: Clinical Benefit Rate: Percentage of Participant who Achieved a Response of Stable Disease (SD), Partial Response (PR) or Complete Response (CR) [ Time Frame: Randomization until Date of Disease Progression (PD) or Death (up to 12 Months after last participant randomized) ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: February 2011
Estimated Study Completion Date: March 2015
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1

Cycle 1-2 (21 day cycle):

Day 1: Pemetrexed 500 milligrams per meter square (mg/m^2) and Cisplatin 75 mg/m^2) Day 2: LY2603618 130 - 275 milligrams (mg)

After 2 cycles, participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met.

Drug: Pemetrexed
Administered intravenously
Drug: Cisplatin
Administered intravenously
Drug: LY2603618
Administered intravenously
Experimental: Phase 2: Pemetrexed + Cisplatin + LY2603618

Cycles 1-4 (21 day cycle):

Before 25 October 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 October 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 October 2012:

Day 1: Pemetrexed 500 mg/m^2 Day 2: LY2603618 dose determined from phase 1

After 25 October 2012:

Day 1: Pemetrexed 500 mg/m^2 If, as of 25 October 2012, participants were in maintenance therapy, and randomized to the experimental arm, they are eligible to continue with pemetrexed (Day 1)/ LY2603618 (Day 2) therapy if the investigator deems it is in best interested of the participant and the participants consents

Drug: Pemetrexed
Administered intravenously
Drug: Cisplatin
Administered intravenously
Drug: LY2603618
Administered intravenously
Active Comparator: Phase 2: Pemetrexed + Cisplatin

Cycle 1-4 (21 day cycle):

Day 1: Pemetrexed 500 milligrams per meter square (mg/m^2) and 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

Drug: Pemetrexed
Administered intravenously
Drug: Cisplatin
Administered intravenously

  Eligibility

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

Inclusion Criteria:

  • Phase 1 portion:

    • Participants with a cytologic or histologic diagnosis of nonsquamous Non-small Cell Lung Cancer (NSCLC) which is classified as Stage IV according to the seventh 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 which 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 which is classified as Stage IV according to the seventh edition of the American Joint Committee on Cancer (AJCC) classification
    • Be eligible for a first line of palliative treatment with a platinum doublet
    • Have archived 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 (IND) (Response Evaluation Criteria in Solid Tumors [RECIST]) 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 of less than or equal to one 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 less than 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 less than 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 patient 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 (CT) scan or magnetic resonance imaging (MRI) 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 patient'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
  • Patients taking non-steroidal anti-inflammatory drugs (NSAIDs) 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
  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: NCT01139775

Locations
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, Baden-Wurttemberg, Germany, 68167
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.
Munster, Nordhein-Westfalen, Germany, 48149
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, Sachsen, Germany, 01640
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.
Berlin, Germany, 14165
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, 60596
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, 30625
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.
Heidelberg, Germany, 69126
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.
Homburg, Germany, 66421
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.
Immenhausen, Germany, 34376
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.
Lübeck, Germany, 23538
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.
Mainz, Germany, D-55131
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.
Rheine, Germany, 48431
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.
Ulm, Germany, 89081
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.
Oviedo, Asturias, Spain, 33006
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.
Mataro, Barcelona, Spain, 08304
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, Madrid, Spain, 28223
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.
Barcelona, Spain, 08036
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.
Barcelona, Spain, 08035
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.
Barcelona, Spain, 08908
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.
Girona, Spain, 17007
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, 28046
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, 28034
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, 28050
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.
Sevilla, Spain, 41013
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: NCT01139775     History of Changes
Other Study ID Numbers: 13797, I2I-MC-JMMG
Study First Received: June 1, 2010
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Spain: Ministry of Health

Keywords provided by Eli Lilly and Company:
solid tumors
Mesothelioma
Carcinoma

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

ClinicalTrials.gov processed this record on August 20, 2014