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

MedImmune

Status and phase: Completed; Phase 1

Conditions: Cancer

Treatments: Drug: MEDI-575

Study type: Interventional

Funder types: Industry

Identifiers

NCT00816400

MI-CP187

Details and patient eligibility

About

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.

Enrollment: 49 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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49 participants in 9 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575

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

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575

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

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575

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

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575

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

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575

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

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575

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

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575

MEDI-575, 9.0 mg/kg QWk Expansion Phase

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575

MEDI-575, 25 mg/kg Q3Wk Expansion Phase

Experimental group

Description:

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.

Treatment:

Drug: MEDI-575