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Study of Insulin-like Growth Factor (IGF)-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing IGF-1R

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ClinicalTrials.gov Identifier: NCT02045368
Recruitment Status : Completed
First Posted : January 24, 2014
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
IGF Oncology, LLC

Tracking Information
First Submitted Date  ICMJE January 15, 2014
First Posted Date  ICMJE January 24, 2014
Last Update Posted Date August 22, 2019
Actual Study Start Date  ICMJE January 28, 2014
Actual Primary Completion Date September 30, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2014)
Maximum Tolerated Dose (MTD) [ Time Frame: Up to 30 days after final dose. ]
The primary objective is to determine the maximum tolerated dose (MTD) of 765IGF-MTX by evaluation of toxicity for the treatment of advanced, previously treated malignancies that express IGF-1R.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02045368 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2017)
  • Adverse Effects [ Time Frame: Up to 30 days after last dose study drug. ]
    Characterize adverse effects (AE) of 765IGF-MTX in patients with advanced, previously treated malignancies as defined by CTCAE v 4.0.
  • Disease Response based on RECIST Criteria [ Time Frame: Up to 8 weeks after last dose study drug. ]
    Evaluate clinical response of 765IGF-MTX in patients with advanced, previously treated malignancies. Disease response will be assessed every 8 weeks while on study treatment using the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2014)
  • Adverse Effects [ Time Frame: Up to 30 days after last dose study drug. ]
    Characterize adverse effects (AE) of 765IGF-MTX in patients with advanced, previously treated malignancies.
  • Disease Response based on RECIST Criteria [ Time Frame: Up to 8 weeks after last dose study drug. ]
    Evaluate clinical response of 765IGF-MTX in patients with advanced, previously treated malignancies. Disease response will be assessed every 8 weeks while on study treatment using the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Insulin-like Growth Factor (IGF)-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing IGF-1R
Official Title  ICMJE STM-02: Phase I Study of IGF-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing Insulin-like Growth Factor Receptor 1 (IGF-1R)
Brief Summary This phase I dose escalation study will evaluate IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated tumors. 765IGF-MTX is administered as an IV infusion over 1 hour on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, unacceptable toxicity, or patient refusal. Assessment of response will be confirmed with imaging studies performed at the end of cycle 2 +/- 7 days, and every 2 weeks thereafter.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Brain Cancer
  • Gastrointestinal Cancers
  • Genitourinary Cancers
  • Gynecologic Cancers
  • Head and Neck Cancers
  • Melanoma
  • Thoracic Cancers
Intervention  ICMJE Drug: IGF-Methotrexate conjugate
IV infusion at the assigned dose administered on days 1, 8, and 15 of a 28 day (4 week) cycle. Up to 7 dose levels will be tested, starting with 0.05 microequivalents per kg and up to 2.5 microequivalents per kg.
Other Name: 765IGF-MTX
Study Arms  ICMJE Experimental: Subject Treatment with IGF-Methotrexate conjugate
IV infusion at the assigned dose administered on days 1, 8, and 15 of a 28 day (4 week) cycle.
Intervention: Drug: IGF-Methotrexate conjugate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 20, 2019)
92
Original Estimated Enrollment  ICMJE
 (submitted: January 22, 2014)
40
Actual Study Completion Date  ICMJE September 30, 2016
Actual Primary Completion Date September 30, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of advanced malignancy, refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy.
  2. Tumor (tissue, bone marrow, or blood) must express IGF-1R, defined as 10% or higher of cells expressing IGF-1R by immuno-histochemistry (IHC), or 0.1% or higher for IGF-1R expression by flow cytometry (blood or bone marrow aspirate).
  3. Paraffin-embedded tissue sections will be stained with antibodies against insulin-like growth factor receptor 1 (IGFR-1) according to the manufacturer's recommended protocols. IHC staining and flow cytometry will be performed at the Pathology Department of the University of Illinois Cancer Center.
  4. Measurable or evaluable disease per RECIST 1.1 criteria for solid tumors and lymphoma as defined in the protocol. For other hematologic malignancies, see below (measurable disease per RECIST 1.1 criteria not necessary).
  5. Multiple Myeloma: Confirmed diagnosis of multiple myeloma as defined in the protocol with relapsed or refractory disease, and measurable disease defined as one of below:

    • Serum monoclonal protein > 500mg/dL by serum protein electrophoresis (SPEP)
    • Urine monoclonal protein > 200mg/24 hours by urine protein electrophoresis (UPEP)
    • Measurable free light chain by free light chain assay > 10mg/dL with abnormal kappa to lambda light chain ratio
    • Measurable bone disease by > 1 bone lesion which is > 20 mm on conventional techniques or > 10 mm with spiral CT (for lytic lesions)
    • Monoclonal bone marrow plasmacytosis > 30%
  6. Lymphoma: Previously treated, histologically confirmed lymphoma with measurable disease via RECIST 1.1, with the exception of lymphoplasmacytic lymphoma, which can be diagnosed based on morphologic evidence in the bone marrow plus the appropriate paraprotein.
  7. Waldenstrom's Macroglobulinemia: Confirmed diagnosis with relapsed or refractory disease, and measurable disease defined as at least one lesion with a single diameter of greater than 2cm by CT or bone marrow involvement with greater than 10% malignant cells and immunoglobulin (IgM, IgG, IgA) greater than 1000mg/dL.
  8. Hematologic malignancies including myelodysplastic syndrome(MDS), leukemia: Confirmed histologic diagnosis with relapsed or refractory disease; measurable disease per RECIST 1.1 criteria is not required.
  9. Age ≥ 18 years
  10. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  11. Prior systemic chemotherapy, immunotherapy, or biological therapy, radiation therapy and/or surgery are allowed; however prior use of methotrexate allowed if > 6 months prior to study entry. Intrathecal methotrexate is allowed prior to and during treatment per investigator discretion. Time since prior therapy and the first dose of study drug:

    • At least 2 weeks since prior radiation, non cytotoxic small molecule drugs (e.g., tyrosine kinase inhibitors such as erlotinib and hormonal agents such as letrozole), prior major surgery (surgery defined as a surgery involving a risk to the life of the patient; specifically: an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity), prior systemic FDA approved therapy

      • At least 3 weeks since prior antineoplastic therapy
      • At least 4 weeks since exposure to monoclonal antibodies (chimeric or fully human)
      • At least 6 weeks since prior nitrosureas or mitomycin-C
  12. Patient must have recovered from the acute toxic effects (≤ grade 1 CTCAE v.4.0) of previous anti-cancer treatment prior to study enrollment; the only exception is that grade 2 neuropathy is permitted
  13. Adequate organ function within 14 days of study registration defined as the following laboratory values:

    • Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L
    • Hemoglobin ≥ 9g/dL* (Patient may not have had a transfusion within 7 days of blood draw.)
    • Platelets ≥ 100 X 10^9/L* (Patient may not have had a transfusion within 7 days of blood draw.)
    • Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
    • Alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 X ULN < 5 X ULN is acceptable if liver has tumor involvement)
    • Serum creatinine ≤ 1.5 X ULN
    • Creatinine clearance ≥ 60 ml/min^2 or glomerular filtration rate (GFR) ≥ 60 ml/min^2 or 24 hour urine creatinine clearance ≥ 50 ml/min
    • Laboratory values for lymphoma patients:

      • Absolute neutrophil count (ANC) ≥ 1.0 X 10^9/L
      • Hemoglobin ≥ 8g/dL
      • Platelets ≥ 50 X 10^9/L
      • Total bilirubin ≤ 1.5 X ULN
      • Alkaline phosphatase, AST and ALT ≤ 3 X ULN (< 5 X ULN is acceptable if liver has tumor involvement)
      • Serum creatinine ≤ 1.5 X ULN
      • Creatinine clearance ≥ 60 ml/min^2 or GFR ≥ 60 ml/min^2 or 24 hour urine creatinine clearance ≥ 50 ml/min
  14. Negative urine or serum pregnancy test in females. Male and female patients with reproductive potential must use an approved contraceptive method if appropriate (for example, abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier methods) during and for 3 months after the last dose of 765IGF-MTX.
  15. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Exclusion Criteria:

  1. Untreated central nervous system (CNS) metastases
  2. Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
  3. ≥ Grade 3 peripheral neuropathy within 14 days before enrollment.
  4. Systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection.
  5. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  6. Pregnant or breastfeeding - methotrexate is Pregnancy Category X - has been reported to cause fetal death and/or congenital abnormalities. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  7. Uncontrolled diabetes mellitus defined as a Hemoglobin A1C≥ 7% in patients with a prior history of diabetes, 28 days prior to study enrollment.
  8. Serious concomitant systemic disorders (e.g., active infection, uncontrolled diabetes) or psychiatric disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
  9. Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
  10. Recent (within 6 months) arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI).
  11. History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
  12. Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant.
  13. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulants for at least 6 weeks are eligible.
  14. Presence of any non-healing wound, fracture, or ulcer within 28 days prior to the first dose of study drug.
  15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IGF or methotrexate
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02045368
Other Study ID Numbers  ICMJE STM-02
2013-0655 ( Other Identifier: University of Illinois at Chicago (UIC) Office for the Protection of Research Subjects (OPRS) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party IGF Oncology, LLC
Study Sponsor  ICMJE IGF Oncology, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Neeta Venepalli, MD University of Illinois at Chicago
PRS Account IGF Oncology, LLC
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP