Clinical trial NCT01577745: A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Advanced Solid Tumors
Official title: A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Adult Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Cancer
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2012-04-16
Enrollment: 58
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: This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation (3+3) study to evaluate the safety, tolerability, antitumor activity, PK and immunogenicity of MEDI0639.

Detailed description: This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation (3+3) study to evaluate the safety, tolerability, antitumor activity, PK, and immunogenicity of MEDI0639 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exist. Up to 63 subjects will be enrolled at approximately 3 to 5 study centers in North America.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed solid tumors that are refractory to standard therapy or for which no standard therapy exist
* Age ≥ 18 years
* ECOG Performance Status of 0 or 1
* LVEF (measured by Echocardiogram) \> 50%
* No gastrointestinal bleeding within 1 year of study entry.
* Adequate organ and marrow function:

  * Hemoglobin ≥ 10g/dL
  * Absolute Neutrophil Count ≥ 1500/mm3
  * Platelet Count ≥ 100,000/mm3
  * AST \& ALT ≤ 2.5 x ULN
  * Bilirubin ≤ 1.5 x ULN
  * Cr Cl ≥ 50 mL/min (as determined by the Cockcroft-Gault equation or by 24-hour urine collection)
* Prior therapy against VEGF or VEGFRs including, but not limited to bevacizumab, sunitinib, sorafenib, pazopanib, motesanib (AMG706), or cediranib (AZD2171), is permitted so long as the agent does not have any known activity against DLL4 and the last dose received s at least 6 weeks prior to first dose of MEDI0639.
* Life expectancy ≥ 12 weeks
* Females of childbearing potential must be surgically sterile, have a sterile male partner, be premenarchal or at least 2 years postmenopausal, practice abstinence or otherwise must use 2 effective methods of contraception from the time of initiation of investigational product.
* Males, unless surgically sterile, must use 2 effective methods of contraception with a female partner and must agree to continue using such contraception for 90 days after the last dose of MEDI0639

Exclusion Criteria:

* Concurrent enrollment in another investigational clinical study
* Receipt of any investigational anticancer therapy within 4 weeks prior to the first dose of MEDI0639 or in the case of monoclonal antibodies, 6 weeks prior to the first dose of MEDI0639
* Concurrent or previous treatment with inhibitors of DLL4
* Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
* Known bleeding diathesis, esophageal varices, or angioplasty
* Pulmonary hemorrhage or gross hemoptysis within 12 months
* Known arterial or venous thrombosis or pulmonary embolism within 2 years
* Concurrent use of systemic low molecular weight heparin or low dose warfarin
* Presence of brain metastases
* Cerebrovascular accident or transient ischemic attack within 2 years
* Cardiovascular events, such as myocardial infarction, unstable/severe angina, coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring medication, congestive heart failure (NYHA \> class II), within 2 years
* Tumors with squamous cell histology
* Major surgical procedure within 90 days
* Pregnancy or lactation
* Known HIV positive or Hepatitis A, B, or C infection

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of MEDI0639
timeFrame: From the first dose of MEDI0639 to 21 days after the first dose
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From the first dose of MEDI0639 until 90 days after the last dose of MEDI0639. Maximum time frame across participants was 11 months.
measure: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From the first dose of MEDI0639 until the end of participation in the study. Maximum time frame across participants was 4 years.
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters
timeFrame: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination
timeFrame: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations
timeFrame: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations
timeFrame: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
Secondary outcomes:
measure: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639
timeFrame: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
measure: Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639
timeFrame: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
measure: Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639
timeFrame: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
measure: Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639
timeFrame: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
measure: Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639
timeFrame: On Day 1 of Cycles 1, 2, 3, and every other cycle thereafter, end of treatment, 30 days, and 3 and 6 months after the last dose of MEDI0639. Maximum time frame across participants was 14 months.
measure: Percentage of Participants With Best Overall Response
timeFrame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
measure: Percentage of Participants With Objective Response
timeFrame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
measure: Percentage of Participants With Disease Control
timeFrame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
measure: Time to Response
timeFrame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
measure: Duration of Response (DR)
timeFrame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
measure: Progression-free Survival (PFS)
timeFrame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
measure: Overall Survival
timeFrame: From study entry through the end of the study. Maximum time frame across participants was 4 years.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: New York
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Houston
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
Study officials:
References: