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A Study in Non Small Cell Lung Cancer

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.

Tracking Information
First Received DateJune 1, 2010
Last Changed DateMay 16, 2018
Start DateFebruary 2011
Actual Primary Completion DateMay 2013
Primary Outcome Measures

Phase 2: Progression-Free Survival Time [Time Frame: Randomization up to first date of PD or death from any cause (up to 6 months after the last participant entered treatment)]

Phase 1: Recommended Phase 2 Dose of LY2603618 [Time Frame: Time of first dose to last dose]

Secondary Outcome Measures

Phase 2: Overall Survival [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)]

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 (up to 6 months after the last participant was randomized)]

Phase 2: Change in Tumor Size [Time Frame: Baseline, end of Cycle 2]

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

Phase 1: Pharmacokinetic: Cmax (Pemetrexed and Cisplatin) [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.]

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

Phase 1: Pharmacokinetic: AUC (Pemetrexed and Cisplatin) [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.]

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]

Phase 2: Pharmacokinetic: AUC (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]

Phase 2: Change From Baseline to Long-term Follow up in Lung Cancer Symptom Scale (LCSS) [Time Frame: Randomization to the end of study (approximately 12 months after the last participant entered treatment)]

Phase 1: Document Any Antitumor Activity Per Radiological Scans and/or Tumor Markers [Time Frame: Baseline through end of Phase 1]

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 or death (up to 6 months after the last participant was randomized)]

Descriptive Information
PhasePhase 1/Phase 2
Study TypeInterventional
Condition
  • Non Small Cell Lung Cancer
Intervention
  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: LY2603618
Study Arms / Comparison Groups3 / 0
Recruitment Information
Recruitment StatusCompleted
Actual Enrollment76
GenderAll
Ages18 Years - N/A
Accepts Healthy VolunteersNo
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

Administrative Information
NCTIDNCT01139775
Responsible PartySponsor
SponsorEli Lilly and Company
Verification DateMay 2018
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