A Phase 1 Study in Patients With Solid Tumors

Phase 1

Completed

Conditions: Solid Tumors

Interventions: Drug: LY573636
Drug: Pemetrexed

Registration Number: NCT01215916

Lead Sponsor: Eli Lilly and Company

Brief Summary: The primary objective of this study is to determine the maximum tolerated dose (MTD) regimen for the combination therapy of LY573636 and pemetrexed that may be safely administered to patients with a solid tumor that is not amenable to curative therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 39

Inclusion Criteria

You must have a diagnosis of a solid tumor malignancy that is not amenable to curative therapy
You must have a serum albumin level greater than or equal to 3.0 grams per deciliter (g/dL) [30 grams per liter (g/L)]
You must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
You must be reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures
Patients with reproductive potential should use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drugs
Your test results assessing the function of your blood, kidneys, liver, and heart are satisfactory
You must be willing to take folic acid, Vitamin B12, or prophylactic steroids
You must able to interrupt the use of aspirin (other than an aspirin dose less than or equal to 1.3 grams per day) and/or other nonsteroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents, such as piroxicam)
You must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, hormone therapy, or other investigational therapy for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy (except alopecia). Patients who have received whole-brain radiation must wait 90 days before starting study therapy.
You must sign an informed consent

Exclusion Criteria

You cannot have received other investigational drugs within the last 30 days
You cannot have other on-going serious illnesses including active bacterial, fugal, or viral infections
You cannot require regular, periodic paracentesis or thoracentesis
You cannot have active brain metastasis
You cannot currently be receiving warfarin (Coumadin®) therapy
You cannot be pregnant or lactating
You cannot have received prior pemetrexed or LY573636
You cannot have a second primary malignancy that could affect interpretation of the study results

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental: Pemetrexed followed by LY573636	LY573636	Pemetrexed on Day 1 followed by LY573636 on Day 4
Experimental: Pemetrexed followed by LY573636	Pemetrexed	Pemetrexed on Day 1 followed by LY573636 on Day 4
Experimental: LY573636 followed by Pemetrexed	LY573636	LY573636 on Day 1, pemetrexed on Day 4
Experimental: LY573636 and Pemetrexed on Day 1	LY573636	LY573636 and Pemetrexed on Day 1
Experimental: LY573636 followed by Pemetrexed	Pemetrexed	LY573636 on Day 1, pemetrexed on Day 4
Experimental: LY573636 and Pemetrexed on Day 1	Pemetrexed	LY573636 and Pemetrexed on Day 1

Primary Outcome Measures

Name	Time	Method
Recommended Phase 2 Dose	Baseline to toxicity [up to end of Cycle 1 (cycle = 21 or 28 days)]	Based on maximum tolerated dose (MTD) in Cycle 1: highest dose where \<33% participants (pts) had dose-limiting toxicity (DLT). DLTs were adverse events (AE) possibly related to study drug or AEs that met any of National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTAE): Grade (G) 4 neutropenia lasting ≥5 days; G4 neutropenia with fever, G4 thrombocytopenia, G3 thrombocytopenia with bleeding, ≥G3 non-hematologic toxicity (except nausea/vomiting and diarrhea controlled by medication; electrolyte toxicity resolved with standard replacement treatment; alopecia; and elevated alanine aminotransferase or aspartate aminotransferase with preexisting hepatic metastasis, if agreed by investigator). Investigators, with sponsor, could declare a DLT if pt experienced increasing toxicity during treatment and it was clear that further treatment would expose pt to excessive risk. Enrollment was stopped during the dose-escalation phase, thus further dose-escalation was not explored.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Significant Effects	Baseline to end of study (up to 1 year of treatment plus 30-day follow-up)	Clinically significant effects were defined as serious and other non-serious adverse events (AEs) regardless of causality. A summary of serious and all other non-serious AEs is located in the Reported Adverse Events module.
Percentage of Participants With a Tumor Response	Baseline to progressive disease (up to 1 year of treatment plus 30-day follow-up)	Tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and confirmed by repeat assessment. Complete Response (CR) was defined as the disappearance of all target lesions and the normalization of tumor marker levels for non-target lesions; Partial Response (PR) was defined as at least a 30% decrease in the sum of the longest diameter of target lesions. Percentage of participants with a tumor response = (number of participants with CR or PR/number of enrolled participants)\*100.
Pharmacokinetics, Concentration Maximum (Cmax) of LY573636	Cycles 1 and 2 on Day 4 (prior to and at the end of LY573636 infusion, 2 and 4 hours post LY573636 infusion), Day 8 (anytime), Day 15 (anytime)
Pharmacokinetics, Area Under the Curve (AUC) of LY573636	Cycles 1 and 2 on Day 4 (prior to and at the end of LY573636 infusion, 2 and 4 hours post LY573636 infusion), Day 8 (anytime), Day 15 (anytime)	Area under the concentration-time curve above the albumin corrected threshold (AUCalb) is provided for LY573636, which has been found to be highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) LY573636.

Trial Locations

Locations (1): 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.
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New Brunswick, New Jersey, United States