A Study of IMC-TR1 in Patients With Advanced Solid Tumors

This study is currently recruiting participants.
Verified August 2013 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01646203
First received: June 11, 2012
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

A study to evaluate the safety and tolerability of IMC-TR1 in patients with advanced solid tumors, as well as gather evidence of anti-tumor activity.


Condition Intervention Phase
Neoplasms
Tumor
Biological: IMC-TR1
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of Anti-TGFβRII Monoclonal Antibody IMC-TR1 (LY3022859) in Patients With Advanced Solid Tumors That Have Failed Standard Therapy or for Which No Standard is Available

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Recommended phase 2 dose of IMC-TR1 [ Time Frame: Baseline to study completion (Approximately 18 Months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of IMC-TR1 [ Time Frame: Baseline through Cycle 1 (6 weeks) ] [ Designated as safety issue: No ]
  • Number of Dose-Limiting Toxicities (DLTs) [ Time Frame: Baseline through Cycle 1 (6 weeks) ] [ Designated as safety issue: No ]
  • Immunogenicity - Development of antibodies against IMC-TR1 [ Time Frame: Cycle 1 - Day 1 and Day 29, Cycle 2 - Day 15, Cycle 3 and each consecutive cycle - Day 1 ] [ Designated as safety issue: No ]
  • Antitumor activity of IMC-TR1 as monotherapy, assessed via tumor measurement by Response Evaluation Criteria in Solid Tumors, Version 1.1 [ Time Frame: Day 36 of every cycle and at 30 day follow-up ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Area under the concentration-time curve (AUC) of IMC-TR1 [ Time Frame: 0, 1, 2, 4, 8, 24, 48, 96,168, and 336 hours after the first and fifth infusion ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Maximum concentration (Cmax) of IMC-TR1 [ Time Frame: 0, 1, 2, 4, 8, 24, 48, 96,168, and 336 hours after the first and fifth infusion ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Minimum concentration (Cmin) of IMC-TR1 [ Time Frame: 0, 1, 2, 4, 8, 24, 48, 96,168, and 336 hours after the first and fifth infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 95
Study Start Date: July 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-TR1

Part A - Dose Escalation:

Cohort 1A: 1.25 mg/kg, intravenously (IV), every 2 weeks of the 6-week treatment cycle

Cohorts 1B-9: Dose Escalation from 12.5 mg to 1600 mg (flat dose), intravenously (IV), every 2 weeks of the 6-week treatment cycles

Cohorts 10-12: Dose escalation from 800 mg to 1600 mg (flat dose), intravenously (IV), weekly during the 6-week treatment cycles

Part B - Disease Specific Cohort Expansion:

Patients will be enrolled into each of three tumor-specific cohort expansions. Patients will be treated with recommended Phase 2 dose.

Biological: IMC-TR1
Administered intravenously
Other Name: LY3022859

Detailed Description:

This is the first-in-human Phase 1 study of IMC-TR1.

  Eligibility

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

Inclusion Criteria:

  • Part A and Part B: Patients must be appropriate candidates for experimental therapy, with a solid tumor that has failed standard therapy or for which no standard therapy is available, and evidence of progressive disease

    • Part A only: Patients must have histological or cytological evidence of a solid tumor which is advanced and/or metastatic
    • Part B only: Patient who have failed first-line therapy/standard of care and have histological or cytological evidence of a cancer type for which evidence of activity was observed during Part A or for which preclinical evidence of potential activity has been observed
  • Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

    • Part A only: Patients may have measurable or nonmeasurable disease
    • Part B: Patients must have measurable disease
  • Have adequate organ function including: Hematologic, Hepatic, Albumin, Coagulation and Renal function
  • Have a performance status of ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Have discontinued previous treatments for cancer and recovered from the acute effects of therapy
  • Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug
  • Females with child bearing potential must have had a negative serum pregnancy test and must not be breastfeeding
  • Have an estimated life expectancy that is > 3 months

Exclusion Criteria:

  • Have clinically significant cardiac disease, including:

    • Myocardial infarction within 6 months prior to study entry, unstable angina pectoris, congestive heart failure, or uncontrolled hypertension
    • Major electrocardiogram (ECG) abnormalities
    • Major abnormalities documented by echocardiography with Doppler
    • Have known predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress
    • Have QTc interval of > 500 msec on screening ECG
  • Have other known serious pre-existing medical conditions
  • Have received prior investigational therapy targeting TGFβ or its receptors
  • Have a known sensitivity to monoclonal antibodies or other therapeutic proteins, to agents of similar biologic composition as IMC-TR1
  • Have a high risk of gastrointestinal bleeding, active inflammatory bowel disease, or chronic steroid use
  • Are currently using or has received a systemic thrombolytic agent within 28 days prior to enrollment
  • Are receiving:

    • full-dose warfarin • intravenous heparin or low-molecular-weight heparin • chronic daily treatment with aspirin at a dose greater than 325 mg per day or nonsteroidal anti-inflammatory medications known to inhibit platelet function

  • Have evidence of retinal disease or are a monocular patient
  • Have received a solid organ transplant, bone marrow transplant or stem cell transplant
  • Have symptomatic central nervous system (CNS) malignancy or untreated metastasis
  • Have acute or chronic leukemia
  • Have a known active fungal, bacterial, and/or viral infection including human immunodeficiency virus or viral hepatitis requiring treatment
  • Has a positive fecal occult blood test within 14 days prior to enrollment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01646203

Contacts
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Locations
United States, Tennessee
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 Recruiting
Nashville, Tennessee, United States, 37232
Contact: ImClone         
United States, Texas
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 Recruiting
Houston, Texas, United States, 77030
Contact: ImClone         
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 Recruiting
San Antonio, Texas, United States, 78229
Contact: ImClone         
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01646203     History of Changes
Other Study ID Numbers: 14549, I5I-IE-JTCA
Study First Received: June 11, 2012
Last Updated: August 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Advanced Solid Tumors

Additional relevant MeSH terms:
Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014