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

Primary Purpose

Epithelial Tumors, Malignant

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MEHD7945A
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epithelial Tumors, Malignant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Uni of Colorado Cancer Center; Anschutz Cancer Pavilion
  • Massachusetts General Hospital.
  • University of Texas M.D. Anderson Cancer Center
  • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
  • Hospital Clinico Universitario de Valencia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Dose Escalation (MEHD7945A)

Dose Expansion (MEHD7945A)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With Dose-Limiting Toxicities (DLTs) of MEHD7945A
Maximum Tolerated Dose (MTD) of MEHD7945A
Percentage of Participants With Adverse Events
Percentage of Participants With Anti-MEHD7945A Antibodies

Secondary Outcome Measures

Area Under the Concentration-Time Curve (AUC) of MEHD7945A
Maximum Serum Concentration (Cmax) of MEHD7945A
Minimum (Trough) Concentration (Cmin) of MEHD7945A
Clearance (Cl) of MEHD7945A
Volume of Distribution at Steady State (Vss) of MEHD7945A
Half-Life (t1/2) of MEHD7945A
Accumulation Ratio of MEHD7945A
Recommended Phase 2 Dose (RP2D) of MEHD7945A
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)
Duration of Objective Response (CR or PR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0)
Progression-Free Survival (PFS) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0)

Full Information

First Posted
September 20, 2010
Last Updated
April 30, 2018
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01207323
Brief Title
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

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
November 9, 2010 (Actual)
Primary Completion Date
December 3, 2013 (Actual)
Study Completion Date
April 23, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epithelial Tumors, Malignant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation (MEHD7945A)
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Expansion (MEHD7945A)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MEHD7945A
Intervention Description
MEHD7945A will be administered as specified in the individual arms.
Primary Outcome Measure Information:
Title
Percentage of Participants With Dose-Limiting Toxicities (DLTs) of MEHD7945A
Time Frame
Days 1-28
Title
Maximum Tolerated Dose (MTD) of MEHD7945A
Time Frame
Days 1-28
Title
Percentage of Participants With Adverse Events
Time Frame
Baseline up to approximately 6.75 years
Title
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 Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
Recommended Phase 2 Dose (RP2D) of MEHD7945A
Time Frame
Days 1-28
Title
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)
Title
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)
Title
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Pirzkall, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Uni of Colorado Cancer Center; Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Massachusetts General Hospital.
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Texas M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hospital Univ Vall d'Hebron; Servicio de Oncologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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