Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

A Study of the Safety and Pharmacokinetics (PK) of MEHD7945A in Participants With Locally Advanced or Metastatic Epithelial Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01207323
First received: September 20, 2010
Last updated: April 11, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Epithelial Tumors, Malignant
Drug: MEHD7945A
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Dose-Limiting Toxicities (DLTs) of MEHD7945A [ Time Frame: Days 1-28 ]
  • Maximum Tolerated Dose (MTD) of MEHD7945A [ Time Frame: Days 1-28 ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 6.75 years ]
  • Percentage of Participants With Anti-MEHD7945A Antibodies [ Time Frame: 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 Outcome Measures:
  • Area Under the Concentration-Time Curve (AUC) of MEHD7945A [ Time Frame: 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) ]
  • Maximum Serum Concentration (Cmax) of MEHD7945A [ Time Frame: 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) ]
  • Minimum (Trough) Concentration (Cmin) of MEHD7945A [ Time Frame: 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) ]
  • Clearance (Cl) of MEHD7945A [ Time Frame: 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) ]
  • Volume of Distribution at Steady State (Vss) of MEHD7945A [ Time Frame: 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) ]
  • Half-Life (t1/2) of MEHD7945A [ Time Frame: 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) ]
  • Accumulation Ratio of MEHD7945A [ Time Frame: 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) ]
  • Recommended Phase 2 Dose (RP2D) of MEHD7945A [ Time Frame: Days 1-28 ]
  • 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) [ Time Frame: 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) ]
  • Duration of Objective Response (CR or PR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0) [ Time Frame: 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) ]
  • Progression-Free Survival (PFS) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0) [ Time Frame: 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) ]

Enrollment: 66
Actual Study Start Date: November 9, 2010
Estimated Study Completion Date: August 31, 2017
Estimated Primary Completion Date: August 31, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation (MEHD7945A)
Participants will receive intravenous (IV) infusion of MEHD7945A in escalating doses Q2W until MTD is reached or up to disease progression as determined by the investigator, intolerable toxicity, withdrawal of consent, or death, whichever occurs first. Approximately 5 dose levels between 1 and 30 mg/kg will be evaluated.
Drug: MEHD7945A
MEHD7945A will be administered as specified in the individual arms.
Experimental: Dose Expansion (MEHD7945A)
Participants will receive IV infusion of MEHD7945A Q2W at or below the MTD (decided from dose escalation part) up to disease progression as determined by the investigator, intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Drug: MEHD7945A
MEHD7945A will be administered as specified in the individual arms.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01207323

Locations
United States, Colorado
Uni of Colorado Cancer Center; Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
United States, Massachusetts
Massachusetts General Hospital.
Boston, Massachusetts, United States, 02114
United States, Texas
University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain, 08035
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
Madrid, Spain, 28050
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Andrea Pirzkall, M.D. Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01207323     History of Changes
Other Study ID Numbers: DAF4873g
GO00765 ( Other Identifier: Genentech, Inc. )
2010-022217-26 ( EudraCT Number )
Study First Received: September 20, 2010
Last Updated: April 11, 2017

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Carcinoma
Neoplasms by Histologic Type
Neoplasms
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017