A Dose Escalation, Dose Expansion Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, in Subjects With Advanced Tumors.

NCT00816400 | Completed Phase 1 Results

• 1 other identifier: MI-CP187
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 5

Brief Summary

Evaluate the safety, tolerability and the tolerated maximum dose of MEDI-575 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.

Conditions

Cancer

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Adverse Events

  An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) are events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 14.1.

  From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks

• Number of Participants With Serious Adverse Events

  A serious AE (SAE) is any AE that results in death, is immediately life threatening, require (or prolong) inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs that emerged after start of study drug were reported. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The SAEs were summarized using MedDRA version 14.1.

  From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks

• Treatment-emergent Adverse Events Related to Laboratory Parameters

  Laboratory evaluations of blood and urine samples were performed, including hematology (complete blood count, differential, and platelet count); serum chemistry (SrChem) aspartate transaminase (AST), alanine transaminase, total bilirubin, creatinine, alkaline phosphatase, sodium, potassium, chloride, phosphorus, calcium, glucose, magnesium, albumin, and lactate dehydrogenase); and routine urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.

  From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks

• Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations

  All 12-lead electrocardiograms (ECGs) performed during the study were obtained in triplicate (ie, 3 ECGs were obtained within a 5-minute time interval) and analyzed. ECG parameters included heart rate (high and low), QT interval, QTcB (corrected QT interval per Bazett's formula), and QTcF (corrected QT interval per Fridericia's formula). Number of participants with TEAEs related to ECG after the start of study drug were reported.

  From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks

• Treatment-emergent Adverse Events Related to Vital Sign Parameters

  Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported.

  From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks

• Maximum Tolerated Dose (MTD)

  For the dose escalation phase, a minimum of 21 evaluable participants (3 participants each in Dose Cohorts 1 through 7) were required for this study if Dose Limiting Toxicities (DLTs) do not occur. If a DLT does occur among the first 3 participants in a cohort, 3 additional participants were to be added to the cohort; 3 more participants were to be added to a cohort to determine the MTD if only 3 participants have been previously treated at that dose. The MTD is the maximum dose at which no more than 1 out of 6 participants experienced a DLT. A DLT is defined as any grade 3 or higher hematologic toxicity or any grade 3 or higher non-hematologic toxicity except grade 3 fever (in the absence of neutropenia) or grade 3 rigors/chills.

  From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks

Secondary Outcomes (13)

• Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax)

  For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.

• PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax)

  For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.

• PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose)

  For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.

• PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough)

  For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.

• PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ)

  For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.

Study Arms (9)

MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1)

EXPERIMENTAL

Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days \[QWk\]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2)

EXPERIMENTAL

MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3)

EXPERIMENTAL

MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4)

EXPERIMENTAL

MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5)

EXPERIMENTAL

MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6)

EXPERIMENTAL

MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days \[Q3Wk\]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7)

EXPERIMENTAL

MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

MEDI-575, 9.0 mg/kg QWk Expansion Phase

EXPERIMENTAL

MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

MEDI-575, 25 mg/kg Q3Wk Expansion Phase

EXPERIMENTAL

MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.

Drug: MEDI-575

Interventions

MEDI-575 DRUG

MEDI-575 as an IV infusion

MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4); MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5); MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6); MEDI-575, 25 mg/kg Q3Wk Expansion Phase; MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1); MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7); MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2); MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3); MEDI-575, 9.0 mg/kg QWk Expansion Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed advanced solid tumor for which no curative or standard therapies exist
• Karnofsky performance status of ≥ 60
• Life expectancy of \>12 weeks
• Adequate hematologic and organ function
• Negative serum pregnancy test (women only)
• Two methods of birth control for female participants of child-bearing potential or male participants with their female partners of child-bearing potential

You may not qualify if:

• Prior chemotherapy or investigational treatment within 4 weeks of study drug administration
• Prior biological or immunological treatment within 6 weeks of study drug administration
• Concurrent therapy for of cancer
• Major surgery within four weeks or minor surgery within two weeks of study drug administration
• History of diabetes or current treatment for diabetes
• New York Heart Association ≥ Grade 2 congestive heart failure
• History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to study entry
• History of other invasive malignancy within 5 years (exceptions are cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that are surgically cured)
• Significant active infection
• Known brain metastases
• Pregnancy or lactation or plans to become pregnant while on study
• Clinically significant abnormality on ECG

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (5)

Research Site

Denver, Colorado, United States

Location

Research Site

Indianapolis, Indiana, United States

Location

Research Site

Las Vegas, Nevada, United States

Location

Research Site

Dallas, Texas, United States

Location

Research Site

Norfolk, Virginia, United States

Location

Related Publications (1)

• Becerra CR, Conkling P, Vogelzang N, Wu H, Hong S, Narwal R, Liang M, Tavakkoli F, Pandya N. A phase I dose-escalation study of MEDI-575, a PDGFRalpha monoclonal antibody, in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Nov;74(5):917-25. doi: 10.1007/s00280-014-2567-9. Epub 2014 Aug 23.

  PMID: 25149088 BACKGROUND

Related Links

• MEDI-575\_CP-187\_Protocol\_Redacted\_28Aug14
• PMCID: PMC3749129: Circulating Tumor Cells: Application as a Biomarker for Molecular Characterization and Predictor of Survival in an All-Comer Solid Tumor Phase I Clinical Study

MeSH Terms

Conditions

Neoplasms

Interventions

Tovetumab

Results Point of Contact

• Title: A Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575
• Organization: MedImmune

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2008
• First Posted: January 1, 2009
• Study Start: March 2, 2009
• Primary Completion: January 19, 2012
• Study Completion: January 19, 2012
• Last Updated: June 26, 2018
• Results First Posted: April 11, 2017

Record last verified: 2018-04

Locations

US (5)