A study of LY2603618 with Pemetrexed and Cisplatin in patients with lung cancer

• Conditions: • Histological diagnosis of Stage IV NSCLC other than predominantly squamous cell histology. • Mesothelioma in advanced or metastatic stage for whom the combination with pemetrexed and cisplatin is deemed to be appropriate. • Solid tumors with no other standard therapeutic option with =2previous systemic chemotherapies for their disease and a maximum of 6 cyclesof alkylating agents in all previous therapy settings; MedDRA version: 16.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 16.0Level: LLTClassification code 10025055Term: Lung cancer non-small cell stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-020408-31-DE
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-17
• Last Update Posted: 16 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 125

Inclusion Criteria

•Patients with a cytologic or histologic diagnosis of nonsquamous 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.
• Patients with histologic or cytologic diagnosis of malignant mesothelioma which is unresectable
• Patients 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:
• Have a Histological diagnosis of Stage IV NSCLC other than predominantly squamous cell histology (will subsequently be referred to as nonsquamous NSCLC for ease of reference) which is classified as Stage IV according to the seventh edition of the AJCC classification
• Nonsquamous histology includes the histology of adenocarcinoma, large cell, and others (NSCLC and not otherwise specified [NOS] (Scagliotti et al. 2008; Ciuleano et al. 2009). Patients with large cell-tumours with neuroendocrine differentiation are not eligible)
• Be eligible for a first line of palliatative treatment with a platinum doublet and
have not received any prior systemic chemotherapy, immunotherapy, targeted therapy or biological therapy for NSCLC. Previous adjuvant therapy is not allowed.
• Have archived tumor tissue or tissue from a fresh tumor biopsy. Cytology specimens are not allowed. The biopsy material should correspond to untreated tumor. If a patient has received prior radiotherapy, the patient is eligible only if a new biopsy has been obtained before entering this trial as part of the standard diagnostic plan for the patient
• Phase 1 patients can have measurable or nonmeasurable disease. Phase 2 patients must have at least 1 measurable lesion according to Investigational New Drug (IND) (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) 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 of =1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Males or females at least 18 years of age
• Have given written informed consent prior to any study-specific procedures
• Have adequate organ function including:
• Hematologic: Absolute neutrophil count (ANC) =1.5 x 109/L, platelets =100 x 109/L, and hemoglobin =9 g/dL. Transfusions are allowed to meet this requirement.
• Hepatic: bilirubin =1.5 times the upper limit of normal (ULN); alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) =3 times ULN (AP, AST, and ALT =5 times ULN is acceptable if liver has tumor involvement).
• Renal: Calculated creatinine clearance (CrCl) (Cockcroft-Gault formula; see Protocol Attachment JMMG.4), =45 mL/min. Patient can also be enrolled based on measured CrCl according to local laboratory values. In case of discrepancy between measured and calculated CrCl, the measured value will be considered for enrollment.
[9]Prior radiation therapy for treatment of cancer is allowed to <25% of the bone marrow (Christy and Eckerman 1987), and patients 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

Exclusion Criteria

• Are currently enrolled in, or discontinued within the last 28 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
• 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 patient 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
• Females who are pregnant or lactating
• Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). Testing is not required unless circumstances warrant confirmation.
• Have previously completed or withdrawn from this study or any other study investigating LY2603618 or any other Chk1 inhibitor.
• Have known allergy to pemetrexed, cisplatin, LY2603618, or any ingredient of pemetrexed, cisplatin, or LY2603618 (like Captisol®; CYDEX Pharmaceuticals, Inc.)
• 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 (see Section 9.8).
• 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). One extra line of adjuvant/neoadjuvant chemotherapy will be allowed if it was completed 1 year prior to enrollment. There is no limitation in the number of previous targeted agents (approved or investigational) if they do not have significant bone marrow toxicity.
• Have received more than 6 cycles of therapy containing an alkylating agent.
•Have had a prior malignancy other than NSCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score =6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified