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LY2275796 in Advanced Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00903708
First received: May 15, 2009
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

Primary Objective:

  • To determine a recommended Phase 2 dose of LY2275796 that may be safely administered to patients with advanced cancer, with prospects for therapeutic biologic effects. This will require simultaneous:
  • monitoring of toxicities & determination of maximal tolerated dose (MTD)
  • detecting eIF-4E target inhibition in tumor
  • pharmacokinetic measurements

Secondary Objectives:

  • To estimate pharmacokinetic parameters of LY2275796 and explore pharmacokinetic/pharmacodynamic relationships
  • To document any antitumor activity observed with LY2275796

Condition Intervention Phase
Advanced Cancers
Drug: LY2275796
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose-Escalation, Pharmacokinetic and Pharmacodynamic Evaluation of Intravenous LY2275796 in Patients With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of LY2275796 [ Time Frame: Dose toxicity with each loading dose (daily for 3 days) then weekly ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) defined as highest dose at which 0-1/6 patients experience Grade III toxicity with LY2275796 administered IV as a loading dose daily over 3 days, then as maintenance dose weekly.


Enrollment: 24
Study Start Date: September 2006
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2275796 Drug: LY2275796
100 mg administered by vein as a loading dose daily over 3 days, and then as a maintenance dose weekly thereafter.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Evidence of histologically or cytologically documented malignancy, including patients with treated, stable brain metastases. For Part A: Malignancy that is advanced and/or metastatic for which no proven therapy exists (for example, there is no comparable or satisfactory alternative drug or other therapy available to treat that stage of the disease). For Part B and C: Malignancy that is advanced and/or metastatic for which no proven therapy exists, and presents with disease that is amenable to serial measurement of pharmacodynamics by biopsy.
  2. Male or female >/= 18 years of age
  3. Written informed consent from the patient
  4. Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
  5. Patients must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, or other investigational therapy for at least 4 weeks (2 weeks for palliative radiotherapy, 6 weeks for mitomycin C or nitrosoureas), prior to study enrollment and have recovered from the acute effects of therapy.
  6. Patients are able to comply with the protocol requirements and are reliable and willing to make themselves available for the duration of the study and will abide by the research units policies and procedures.
  7. Have adequate organ function including: Bone Marrow Reserve: Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L prior to treatment, platelets >/= 100 x 10^9/L, hemoglobin >/= 9 g/dL; Hepatic: Bilirubin </= upper limits or normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) </= 2.5 x ULN; Renal: Calculated creatinine clearance by Cockcroft-Gault formula >/= 50 ml/min; Coagulation: Activated prothrombin time (APTT) and prothrombin time (PT) less than or equal to the ULN.
  8. Males and females with reproductive potential should use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug.

Exclusion Criteria:

  1. Patient with current hematological malignancies or bleeding diathesis
  2. Serious pre-existing medical conditions at the discretion of the investigator
  3. Major surgery within 4 weeks of study enrollment
  4. Women who are pregnant or lactating
  5. Symptomatic central nervous system (CNS) neoplasm. (Patients who have CNS neoplasms stable on steroid medication may be included.)
  6. Concomitant anticancer therapy or anticoagulant therapy (with the exception of the use of heparinized saline to maintain the patency of central venous catheters).
  7. Patients who require palliative radiotherapy at the time of study entry
  8. Previous treatment with antisense therapies
  9. Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication
  10. Presence of positive test results in HIV antibodies, Hepatitis B surface antigen, or Hepatitis C antibodies (Rationale: Correlative biologic studies entail aerosolization of biologic fluids. Researchers use Universal precautions and should be protected from HIV or Hepatitis viruses. However, robotic equipment handling specimens with high viral load would require purging and sterilization procedures that could damage the equipment or alter results for subsequent specimens. Patients lacking symptoms or signs of HIV or hepatitis have low viral loads so that screening for them is not necessary).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903708

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: David Hong, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00903708     History of Changes
Other Study ID Numbers: 2005-0770
Study First Received: May 15, 2009
Last Updated: July 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
LY2275796
Eukaryotic initiation factor 4E
eIF-4E

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014