Overview

This trial is active, not recruiting.

Condition non small cell lung cancer
Treatments pemetrexed, cisplatin, ly2603618
Phase phase 1/phase 2
Sponsor Eli Lilly and Company
Start date February 2011
End date May 2013
Trial size 63 participants
Trial identifier NCT01139775, 13797, I2I-MC-JMMG

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
pemetrexed
Administered intravenously
cisplatin
Administered intravenously
ly2603618
Administered intravenously
(Experimental)
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
pemetrexed
Administered intravenously
cisplatin
Administered intravenously
ly2603618
Administered intravenously
(Active Comparator)
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
pemetrexed
Administered intravenously
cisplatin
Administered intravenously

Primary Outcomes

Measure
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)
Phase 1: Recommended Phase 2 Dose of LY2603618
time frame: Time of First Dose to Last Dose

Secondary Outcomes

Measure
Phase 2: Overall Survival
time frame: Randomization to the Date of Death from Any Cause (up to 12 Months after last participant entered treatment)
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)
Phase 2: Change in Tumor Size
time frame: Baseline, End of Cycle 2
Phase 1: Pharmacokinetic: Maximum Concentration (Cmax) (Pemetrexed, Cisplatin and LY2603618)
time frame: Cycle 1 and Cycle 2 of Phase 1
Phase 1: Pharmacokinetic: Area Under the Curve (AUC) (Pemetrexed,Cisplatin and LY2603618)
time frame: Cycle 1 and Cycle 2 of Phase 1
Phase 2: Pharmacokinetic: Maximum Concentration (Cmax) (LY2603618)
time frame: Cycle 1 of Phase 2
Phase2: Pharmacokinetic: Area Under the Curve (AUC) (LY2603618)
time frame: Cycle 1 of Phase 2
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)
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)
Phase 2: Proportion of Participants Receiving Maintenance Therapy
time frame: Cycle 5
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)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in April 2014.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.