Clinical trial NCT00816361: A Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-573 in Subjects With Advanced Solid Tumors
Official title: A Phase 1, Multicenter, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-573, a Fully Human Monoclonal Antibody Directed Against Insulin-like Growth Factors I and II, 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: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Evaluate the safety and tolerability of MEDI-573 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 ≥60.
* Adequate hematological function.
* Adequate organ function.
* Women of non-child-bearing potential (defined as being \>1 year post-menopausal) or using effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the investigational product may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, or total abstinence, from the time the informed consent is signed through 30 days after the last dose of MEDI-573. Male subjects with partners of child-bearing potential must be surgically sterile or use contraceptive method as described above from the time of the initiation of MEDI-573 through 30 days after the last dose of MEDI-573.

Exclusion Criteria:

* No prior treatment within 4 weeks of study drug administration.
* No concurrent therapy for treatment of cancer.
* No uncontrolled 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.
* Documented brain metastasis.
* Pregnancy or lactation or plans to become pregnant while on study.
* Clinically significant abnormality on ECG.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
timeFrame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
measure: Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs
timeFrame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
measure: Maximum Tolerated Dose (MTD) of MEDI-573
timeFrame: Cycle 1 Day 1 through Cycle 1 Day 21
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1 Day 1 through Cycle 1 Day 21
measure: Optimal Biologically Effective Dose (OBED) of MEDI-573
timeFrame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) After the First Dose
timeFrame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
measure: Time to Reach Maximum Observed Concentration (Tmax) After the First Dose
timeFrame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
measure: Trough Serum Concentration (Ctrough) After the First Dose
timeFrame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
measure: Dose Normalized Cmax (Cmax/Dose) After the First Dose
timeFrame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
measure: Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ)
timeFrame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
measure: Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose)
timeFrame: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573
timeFrame: Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
measure: Objective Response Rate (ORR)
timeFrame: From study entry through the end of the study, up to 3.5 years
measure: Progression-free Survival (PFS)
timeFrame: From study entry through the end of the study, up to 3.5 years
measure: Time to Progression
timeFrame: From study entry through the end of the study, up to 3.5 years
measure: Overall Survival
timeFrame: From study entry through the end of the study, up to 3.5 years
measure: Time to Response (TTR)
timeFrame: From study entry through the end of the study, up to 3.5 years
measure: Duration of Response
timeFrame: From study entry through the end of the study, up to 3.5 years
measure: Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573
timeFrame: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
Study officials:
affiliation: MedImmune LLC
name: Susan Perez, MD, MSc
role: STUDY_DIRECTOR
References: