Clinical trial NCT00816400: A Dose Escalation, Dose Expansion Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, in Subjects With Advanced Tumors.
Official title: A Phase 1, Multicenter, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, a Fully Human Monoclonal Antibody Directed Against Platelet-derived Growth Factor Receptor Alpha (PDGFRα), in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2009-01-01
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
measure: Number of Participants With Serious Adverse Events
timeFrame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
measure: Treatment-emergent Adverse Events Related to Laboratory Parameters
timeFrame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
measure: Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations
timeFrame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
measure: Treatment-emergent Adverse Events Related to Vital Sign Parameters
timeFrame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
measure: Maximum Tolerated Dose (MTD)
timeFrame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Secondary outcomes:
measure: Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax)
timeFrame: 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.
measure: PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax)
timeFrame: 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.
measure: PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose)
timeFrame: 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.
measure: PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough)
timeFrame: 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.
measure: PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ)
timeFrame: 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.
measure: PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose)
timeFrame: 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.
measure: Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit
timeFrame: Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks
measure: Percentage of Participants With Objective Response
timeFrame: From study entry through the end of the study, up to 34 months
measure: Time to Response
measure: Duration of Response
measure: Time to Progression
timeFrame: Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months
measure: Progression-free Survival
timeFrame: Start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause whichever occurs first, up to 24 months
measure: Overall Survival
timeFrame: From the start of treatment with MEDI-575 until death or end of study, up to 33 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Norfolk
country: United States
facility: Research Site
state: Virginia
Study officials:
References:
citation: 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.