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

Epithelial Tumors, Malignant Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01207323
• Other study ID #: DAF4873g
• Secondary ID: GO007652010-0222
• Status: Completed
• Phase: Phase 1
• Start date: November 9, 2010
• Est. completion date: April 23, 2018

Study information

• Verified date: April 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: April 23, 2018
• Est. primary completion date: December 3, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Epithelial Tumors, Malignant
• Neoplasms, Glandular and Epithelial

Intervention

Drug:
• MEHD7945A
MEHD7945A will be administered as specified in the individual arms.

Locations

Country	Name	City	State
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	Uni of Colorado Cancer Center; Anschutz Cancer Pavilion	Aurora	Colorado
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

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