Clinical trial NCT01207323: A Study of the Safety and Pharmacokinetics (PK) of MEHD7945A in Participants With Locally Advanced or Metastatic Epithelial Tumors
Official title: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MEHD7945A Administered Intravenously to Patients With Locally Advanced or Metastatic Epithelial Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epithelial Tumors, Malignant
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2010-09-22
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase I, multicenter, open-label study of MEHD7945A in participants with incurable, locally advanced, or metastatic epithelial malignancies that have progressed despite standard therapy or for which no standard therapy exists. The study will be conducted in two stages: a dose escalation stage and an expansion stage. The dose-escalation stage is designed to evaluate the safety, tolerability, and PK of MEHD7945A administered (at five dose levels from 1 to 30 milligrams per kilogram \[mg/kg\]) every 2 week (Q2W). An expansion stage will be initiated after establishment of maximum tolerated dose (MTD) in dose escalation stage. Participants with refractory or recurrent metastatic colorectal cancer (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and pancreatic cancer will be enrolled in an expansion stage to better characterize the safety, tolerability, PK and preliminary assessment of the anti-tumor activity of MEHD7945A.


Eligibility criteria: Inclusion Criteria:

* Life expectancy greater than or equal to (\>/=) 12 weeks
* Availability and willingness to provide sufficient tumor tissue sample for testing
* Dose-escalation stage: Participants with histologically documented incurable, locally advanced, or metastatic epithelial malignancy that has progressed despite standard therapy or for which no standard therapy exists
* Expansion stage: Participants with one of the following epithelial, histologically-documented, incurable, locally advanced, or metastatic tumor that has progressed despite standard therapy or for which no standard therapy exists: CRC, NSCLC, HNSCC, or pancreatic cancer
* Use of an effective means of contraception (e.g., abstinence, hormonal or double barrier method, surgically sterilized partner) for men and women of childbearing potential while enrolled in the study

Exclusion Criteria:

* Less than (\<) 4 weeks since the last anti-tumor therapy prior to Day 1 of study treatment
* Major surgical procedure within 4 weeks prior to Cycle 1, Day 1
* Leptomeningeal disease as the only manifestation of the current malignancy
* Active infection requiring IV antibiotics
* Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs
* Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
* Current severe, uncontrolled systemic disease
* History of cardiac heart failure of any New York Heart Association criteria or serious cardiac arrhythmia requiring treatment
* History of myocardial infarction within 6 months before Cycle 1, Day 1, or history of unstable angina
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
* History of interstitial lung disease
* History of severe allergic or hypersensitivity reaction to other therapeutic antibodies that required discontinuation of therapy
* Known human immunodeficiency virus (HIV) infection
* Primary central nervous system (CNS) malignancy or untreated/active CNS metastases
* Significant traumatic injury within 4 weeks before Cycle 1, Day 1
* Pregnancy or lactation

Primary outcomes:
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs) of MEHD7945A
timeFrame: Days 1-28
measure: Maximum Tolerated Dose (MTD) of MEHD7945A
timeFrame: Days 1-28
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to approximately 6.75 years
measure: Percentage of Participants With Anti-MEHD7945A Antibodies
timeFrame: Baseline up to approximately 6.75 years (assessed at predose [0 to 4 hours {Hr}] on Day 1 [D1] of Cycles [Cy] 1, 2, 4 [1 Cycle: 14 days], at the study completion/early termination (ET) visit [up to approximately 6.75 years])
Secondary outcomes:
measure: Area Under the Concentration-Time Curve (AUC) of MEHD7945A
timeFrame: Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)
measure: Maximum Serum Concentration (Cmax) of MEHD7945A
timeFrame: Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)
measure: Minimum (Trough) Concentration (Cmin) of MEHD7945A
timeFrame: Predose (0 to 4 hours) on D1 of Cy1,2,3,4,6, every 4 Cy thereafter (up to Cy16 ); study completion/ET (up to approximately 6.75 years) (Cy=14 days)
measure: Clearance (Cl) of MEHD7945A
timeFrame: Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)
measure: Volume of Distribution at Steady State (Vss) of MEHD7945A
timeFrame: Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)
measure: Half-Life (t1/2) of MEHD7945A
timeFrame: Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)
measure: Accumulation Ratio of MEHD7945A
timeFrame: Predose (0-4 Hr), 0.5, 4, 24, 72Hr post Cy1 D1 dose (infusion duration=1.5 Hr); Day 8 of Cy 1, 2, 4; predose, 0.5 Hr postose on Day 1 of Cy2, 3, 4, 6, every 4 Cy thereafter (up to Cy16); study completion/ET (approximately 6.75 years) (Cy=14 days)
measure: Recommended Phase 2 Dose (RP2D) of MEHD7945A
timeFrame: Days 1-28
measure: Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0)
timeFrame: From the first study treatment (Cy1 D1, 1 Cy=14 days) to first occurrence of progression or death within 60 days of the last administration of study drug, whichever occurs first (up to approximately 6.75 years)
measure: Duration of Objective Response (CR or PR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0)
timeFrame: First occurrence of a documented objective response until the time of relapse or death within 60 days of the last administration of study drug, whichever occurs first (up to approximately 6.75 years)
measure: Progression-Free Survival (PFS) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0)
timeFrame: From the first study treatment (Cy1 D1, 1 Cy = 14 days) to first occurrence of progression or death within 60 days of the last administration of study drug, whichever occurs first (up to approximately 6.75 years)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Uni of Colorado Cancer Center; Anschutz Cancer Pavilion
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital.
state: Massachusetts
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Genentech, Inc.
name: Andrea Pirzkall, M.D.
role: STUDY_DIRECTOR
References: