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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

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

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

NCT ID

NCT01207323

First Posted

September 20, 2010

Last Updated

April 30, 2018

Sponsor

Genentech, Inc.

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

Arm Title

Dose Expansion (MEHD7945A)

Arm Type

Experimental

Arm Description

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

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

Title

Volume of Distribution at Steady State (Vss) of MEHD7945A

Time Frame

Title

Half-Life (t1/2) of MEHD7945A

Time Frame

Title

Accumulation Ratio of MEHD7945A

Time Frame

Title

Recommended Phase 2 Dose (RP2D) of MEHD7945A

Time Frame

Days 1-28

Title

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

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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