A Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-573 in Subjects With Advanced Solid Tumors

NCT00816361 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MI-CP184
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 6

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.

Conditions

Cancer

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)

  AEs were any unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of MEDI-573, whether or not considered related to MEDI-573. A SAE was any AE that resulted in: death; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; was life-threatening; was a congenital anomaly/birth defect in the offspring of a study participant; or was an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above. TEAEs were defined as AEs present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, up to 30 days after the last dose.

  From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years

• Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs

  An abnormal laboratory finding that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.

  From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years

• Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs

  Vital signs and physical findings included parameters such as heart rate, blood pressure, temperature, and respiratory rate. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573 or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.

  From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years

• Maximum Tolerated Dose (MTD) of MEDI-573

  The MTD was defined as the highest dose that can be safely administered to participants and was determined by the number of participants in each cohort with a dose-limiting toxicity (DLT). The number and proportion of participants in each dose cohort and the number of participants with a DLT was presented using the total number of participants in the MTD Evaluable Population as the denominator. 2 participants from Cohorts 0.5 and 5 mg/kg QWk (1 in each cohort) did not complete the DLT period and therefore not evaluable for MTD.

  Cycle 1 Day 1 through Cycle 1 Day 21

• Number of Participants With Dose-Limiting Toxicities (DLTs)

  A DLT was defined as any grade greater than or equal to (\>=) 3 treatment-related non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: Grade less than (\<) 4 serum-high glucose (fasting) with duration of \< 24 hours; Grade 3 fever (in the absence of neutropenia) defined as \> 40.0 degree centigrade (°C) \[greater than (\>) 104.0°F\] that resolved to normal or baseline within 24 hours of treatment and was not considered an SAE; or Grade 3 rigors/chills that responded to optimal therapy; any Grade \>= 3 treatment-related hematologic toxicity that occurred during the DLT assessment period.

  Cycle 1 Day 1 through Cycle 1 Day 21

• Optimal Biologically Effective Dose (OBED) of MEDI-573

  The OBED was defined as the dose at which all circulating insulin-like growth factor (IGF)-1 and IGF-2 ligand was sequestered by MEDI-573.

  From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years

Secondary Outcomes (14)

• Maximum Observed Serum Concentration (Cmax) After the First Dose

  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

• Time to Reach Maximum Observed Concentration (Tmax) After the First Dose

  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

• Trough Serum Concentration (Ctrough) After the First Dose

  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

• Dose Normalized Cmax (Cmax/Dose) After the First Dose

  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

• Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ)

  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

Study Arms (9)

MEDI-573 0.5 mg/Kg QWk Dose Escalation

EXPERIMENTAL

Participants received MEDI-573 0.5 milligram per kilogram (mg/kg) as a 60-minute intravenous (IV) infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

MEDI-573 1.5 mg/Kg QWk Dose Escalation

EXPERIMENTAL

Participants received MEDI-573 1.5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

MEDI-573 5 mg/Kg QWk Dose Escalation

EXPERIMENTAL

Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

MEDI-573 10 mg/Kg QWk Dose Escalation

EXPERIMENTAL

Participants received MEDI-573 10 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

MEDI-573 15 mg/Kg QWk Dose Escalation

EXPERIMENTAL

Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

MEDI-573 30 mg/Kg Q3Wk Dose Escalation

EXPERIMENTAL

Participants received MEDI-573 30 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

MEDI-573 45 mg/Kg Q3Wk Dose Escalation

EXPERIMENTAL

Participants received MEDI-573 45 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

MEDI-573 5 mg/Kg QWk Dose Expansion

EXPERIMENTAL

Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

MEDI-573 15 mg/Kg QWk Dose Expansion

EXPERIMENTAL

Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.

Drug: MEDI-573

Interventions

MEDI-573 DRUG

Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.

MEDI-573 0.5 mg/Kg QWk Dose Escalation; MEDI-573 1.5 mg/Kg QWk Dose Escalation; MEDI-573 10 mg/Kg QWk Dose Escalation; MEDI-573 15 mg/Kg QWk Dose Escalation; MEDI-573 15 mg/Kg QWk Dose Expansion; MEDI-573 30 mg/Kg Q3Wk Dose Escalation; MEDI-573 45 mg/Kg Q3Wk Dose Escalation; MEDI-573 5 mg/Kg QWk Dose Escalation; MEDI-573 5 mg/Kg QWk Dose Expansion

Eligibility Criteria

• Age: 18 Years - 99 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 ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (6)

Research Site

Scottsdale, Arizona, 85259, United States

Location

Research Site

Jacksonville, Florida, 32224, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

Rochester, Minnesota, 55905, United States

Location

Research Site

Philadelphia, Pennsylvania, 19111, United States

Location

Related Links

• MEDI-573\_CP-184\_Protocol\_Redacted\_16Jul14

MeSH Terms

Conditions

Neoplasms

Interventions

dusigitumab

Results Point of Contact

• Title: Susan Perez MD, MSc
• Organization: MedImmune LLC

information.center@astrazeneca.com

+1 301-398-2827

Study Officials

• Susan Perez, MD, MSc

  MedImmune LLC

  STUDY DIRECTOR

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 9, 2009
• Primary Completion: September 11, 2012
• Study Completion: September 11, 2012
• Last Updated: March 4, 2019
• Results First Posted: March 4, 2019

Record last verified: 2018-10

Locations

US (6)