A Phase 1 Study in Patients With Solid Tumors

NCT01215916 | Completed Phase 1 Results

• 2 other identifiers: 11158H8K-MC-JZAE
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors

Keywords

Solid tumors

Outcome Measures

Primary Outcomes (1)

• Recommended Phase 2 Dose

  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.

  Baseline to toxicity [up to end of Cycle 1 (cycle = 21 or 28 days)]

Secondary Outcomes (4)

• Number of Participants With Clinically Significant Effects

  Baseline to end of study (up to 1 year of treatment plus 30-day follow-up)

• Percentage of Participants With a Tumor Response

  Baseline to progressive disease (up to 1 year of treatment plus 30-day follow-up)

• 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)

Study Arms (3)

Experimental: Pemetrexed followed by LY573636

EXPERIMENTAL

Pemetrexed on Day 1 followed by LY573636 on Day 4

Drug: LY573636; Drug: Pemetrexed

Experimental: LY573636 followed by Pemetrexed

EXPERIMENTAL

LY573636 on Day 1, pemetrexed on Day 4

Drug: LY573636; Drug: Pemetrexed

Experimental: LY573636 and Pemetrexed on Day 1

EXPERIMENTAL

LY573636 and Pemetrexed on Day 1

Drug: LY573636; Drug: Pemetrexed

Interventions

LY573636 DRUG

Individualized dose is dependent on a patient's height, weight, and gender and is adjusted to target a specific exposure range corrected for a patient's laboratory parameters. Intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days). Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Patients are pretreated with folic acid \[350 micrograms (µg) to 1000 µg orally, daily\], Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone \[4 milligrams (mg) orally, twice daily or equivalent\].

Also known as: Tasisulam

Experimental: LY573636 and Pemetrexed on Day 1; Experimental: LY573636 followed by Pemetrexed; Experimental: Pemetrexed followed by LY573636

Pemetrexed DRUG

375 to 500 milligrams per square meter (mg/m\^2), intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days). Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Patients are pretreated with folic acid (350 µg to 1000 µg orally, daily), Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone (4 mg orally, twice daily or equivalent).

Also known as: LY231514, Alimta

Experimental: LY573636 and Pemetrexed on Day 1; Experimental: LY573636 followed by Pemetrexed; Experimental: Pemetrexed followed by LY573636

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (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.

New Brunswick, New Jersey, 08901, United States

Location

MeSH Terms

Interventions

N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide; Pemetrexed

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Limitations and Caveats

Enrollment was stopped early during dose-escalation phase. Original protocol dosed LY573636 and pemetrexed on Day 1; 21-day cycle. Protocol amended (due to dose limiting toxicities); LY573636 and pemetrexed doses separated by 3 days; 28-day cycle.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon.-Fri. 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2010
• First Posted: October 7, 2010
• Study Start: February 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: March 15, 2019
• Results First Posted: March 15, 2019

Record last verified: 2018-12

Locations

US (1)