Conditions

Non Small Cell Lung Cancer

Keywords

solid tumorsMesotheliomaCarcinoma

Outcome Measures

Primary Outcomes (2)

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.
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
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 \[ng/mL\]).
Time of first dose to last dose

Secondary Outcomes (13)

Phase 2: Overall Survival
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)
Randomization until date of disease progression (up to 6 months after the last participant was randomized)
Phase 2: Change in Tumor Size
Baseline, end of Cycle 2
Phase 1: Pharmacokinetic: Maximum Plasma Concentration (Cmax) (LY2603618)
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)
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.
+8 more secondary outcomes

Other Outcomes (1)

Deaths
Randomization through 12 months after the last participant was randomized

Study Arms (3)

Phase 1: LY2603618 130 to 275 mg

EXPERIMENTAL

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.

Drug: PemetrexedDrug: CisplatinDrug: LY2603618

Phase 2: Pemetrexed + Cisplatin + LY2603618

EXPERIMENTAL

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.

Drug: PemetrexedDrug: CisplatinDrug: LY2603618

Phase 2: Pemetrexed + Cisplatin

ACTIVE COMPARATOR

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

Drug: PemetrexedDrug: Cisplatin

Interventions

PemetrexedDRUG

Administered intravenously as a continuous 10-minute infusion

Phase 1: LY2603618 130 to 275 mgPhase 2: Pemetrexed + CisplatinPhase 2: Pemetrexed + Cisplatin + LY2603618

CisplatinDRUG

Administered intravenously as a continuous 1-hour infusion

Phase 1: LY2603618 130 to 275 mgPhase 2: Pemetrexed + CisplatinPhase 2: Pemetrexed + Cisplatin + LY2603618

LY2603618DRUG

Administered intravenously as a continuous 1-hour infusion

Phase 1: LY2603618 130 to 275 mgPhase 2: Pemetrexed + Cisplatin + LY2603618

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.