Clinical trial NCT01248949: A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors
Official title: Phase 1/1b, Open-Label, Dose-Escalation and Expansion Study to Evaluate the Safety and Antitumor Activity of MEDI3617 as a Single-Agent or in Combination Therapy in Adult Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Advanced Recurrent Ovarian Tumors
Keywords: Advanced solid tumors
Advanced recurrent ovarian tumors
MEDI3617
Ang2
Ovarian cancer
Malignant glioma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2010-11-25
Enrollment: 162
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: To determine the maximum tolerated dose or optimal biological dose, and the safety profile of MEDI3617 when given as a single-agent or in combination with other chemotherapeutic agents in subjects with advanced solid malignancies resistant to standard therapy.


Eligibility criteria: Inclusion Criteria:

* Patients with confirmed diagnosis of advanced solid tumors (dose-escalation phase) or another solid tumor type based on antitumoral activity (dose-expansion phase) that are not responsive to standard therapy or for which no standard therapy exists
* Patients must be 18 years of age or older
* Karnofsky Performance Status ≥ 70
* Toxicities from previous cancer therapies must have recovered to CTCAE Grade = or \< 2
* Adequate organ and marrow function
* Using adequate contraceptive measures, be surgically sterile or post-menopausal

Exclusion Criteria:

* Concurrently enrolled in another clinical study, except for non-interventiona observational studies, or if in a follow up period from a previous study
* Receipt of any investigational anticancer therapy within 30 days prior to the first dose of MEDI3617, or in the case of monoclonal antibodies (eg, bevacizumab), 42 days prior to the first dose of MEDI3617
* Current or previous treatment with angiopoietin inhibitors, or inhibitors of Tie1 or Tie2 including, but not limited to, AMG386, CVX-060, XL880, and XL820
* Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
* Use of immunosuppressive medication or systemic steroids within 7 days prior to first dose of MEDI3617
* Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
* Known bleeding diathesis
* Pulmonary hemorrhage or gross hemoptysis within 6 months prior to enrollment
* Therapeutic or palliative radiation therapy within 2 weeks prior to enrollment

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)
measure: Maximum Tolerated Dose (MTD)
timeFrame: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From start of study drug administration up to 90 days after the last dose of MEDI3617
measure: Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs)
timeFrame: From start of study drug administration up to 90 days after the last dose of MEDI3617
measure: Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs)
timeFrame: From start of study drug administration up to 90 days after the last dose of MEDI3617
measure: Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs)
timeFrame: From start of study drug administration up to 90 days after the last dose of MEDI3617
measure: Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs)
timeFrame: From start of study drug administration up to 90 days after the last dose of MEDI3617
measure: Number of Participants With a Decline in Karnofsky Performance Status (KPS) of ≥ 20 Points at Worst Record On-study Compared With Baseline
timeFrame: From start of study drug administration up to 30 days after the last dose of MEDI3617
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of MEDI3617
timeFrame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
measure: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI3617
timeFrame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
measure: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3617
timeFrame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
measure: Systemic Clearance (CL) of MEDI3617
timeFrame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
measure: Terminal Elimination Half Life (t1/2) of MEDI3617
timeFrame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
measure: Number of Participants With Positive Anti-Drug Antibody (ADA)
timeFrame: Presence of ADA to MEDI3617 were assessed prior to infusion with MEDI3617 on Day 1 of each dosing cycle, as well as the end of treatment, and 30 days, 3 months, and 6 months post last dose of MEDI3617
measure: Objective Response Rate (ORR)
timeFrame: Time from the first dose of investigational product until end of study
measure: Time to Response (TTR)
timeFrame: Time from the first dose of investigational product until end of study
measure: Duration of Response (DOR)
timeFrame: Time from the first dose of investigational product until end of study
measure: Time to Progression (TTP)
timeFrame: Time from the first dose of investigational product until end of study
measure: Progression-Free Survival (PFS)
timeFrame: Time from the first dose of investigational product until end of study
measure: Overall Survival (OS)
timeFrame: Time from the first dose of investigational product until death due to any cause
measure: Circulating Levels of Angiopoietin 2 (Ang2)
timeFrame: Prior to infusion on Cycle 4 and Cycle 5
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Lafayette
country: United States
facility: Research Site
state: Indiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
Study officials:
affiliation: MedImmune LLC
name: MedImmune, LLC
role: STUDY_DIRECTOR
References: