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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 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: July 11, 2014
Last verified: July 2014
  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
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: 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: July 11, 2014
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 July 26, 2014