Skip to main content
OpenTrials
Completed

NCT Number: NCT01215916

A Phase 1 Study in Patients With Solid Tumors

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Solid Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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].

Other names: Tasisulam

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).

Other names: LY231514, Alimta

Primary outcomes

  1. Recommended Phase 2 Dose

    Time frame: 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 outcomes

  1. Number of Participants With Clinically Significant Effects

    Time frame: 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.

  2. Percentage of Participants With a Tumor Response

    Time frame: 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.

  3. Pharmacokinetics, Concentration Maximum (Cmax) of LY573636

    Time frame: 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)

  4. Pharmacokinetics, Area Under the Curve (AUC) of LY573636

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

A Phase 1b Study of LY573636-sodium in Combination With Alimta (Pemetrexed) in Patients With Solid Tumors

Important dates

Study start
2008
Primary completion
2011
Study completion
2011
First posted
Oct 7, 2010
Registry last updated
Mar 15, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.