A Study of MNRP1685A in Combination With Bevacizumab With or Without Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of MNRP1685A, a Human IgG1 Antibody, in Combination With Bevacizumab With or Without Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors

This is a Phase Ib, open-label, dose-escalation study of MNRP1685A given by intravenous (IV) infusion as therapy for locally advanced or metastatic solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Cancers
• Intervention / Treatment: Drug: bevacizumab; Drug: paclitaxel; Drug: MNRP1685A

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adequate hematologic and end organ function
• Evaluable disease or measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST)
• Agreement to use an effective form of contraception for the duration of the study

Inclusion Criteria Unique to Arm A:

• Histologically or cytologically documented, incurable, locally advanced, or metastatic solid malignancy that has progressed on, or failed to respond to, at least one prior regimen

Inclusion Criteria Unique to Arm B:

• Histologically or cytologically documented, incurable, locally advanced, or metastatic solid malignancy; a maximum of two prior chemotherapy regimens is allowed

Exclusion Criteria:

• Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks or 5 half-lives (for systemic agents), whichever is shorter, prior to initiation of study treatment with the following exceptions: hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists or antagonists for prostate cancer; herbal therapy > 1 week prior to Day 1; hormone-replacement therapy or oral contraceptives; palliative radiotherapy for bone metastases > 2 weeks prior to Day 1
• Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytics, or a filter of the inferior vena cava
• Leptomeningeal disease as a manifestation of the current malignancy
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of ≤ 10 mg/day prednisone
• Bisphosphonate therapy for symptomatic hypercalcemia
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
• Known human immunodeficiency virus (HIV) infection
• Known primary CNS malignancy, or untreated or active CNS metastases
• Pregnancy, lactation or breast feeding
• Inadequately controlled hypertension
• History of hypertensive crisis or hypertensive encephalopathy
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• New York Heart Association (NYHA) Class II or greater CHF
• History of stroke or transient ischemic attack (TIA) within 6 months prior to Day 1
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy in the absence of stable therapeutic anticoagulation
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to Day 1
• Clinical signs or symptoms of gastrointestinal obstruction or requirement for parenteral hydration, parenteral nutrition, or tube feeding because of an active gastrointestinal condition
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
• Serious, non-healing wound, active gastrointestinal ulcer, or untreated bone fracture
• Intrathoracic lung carcinoma of squamous cell histology
• Grade ≥ 2 sensory neuropathy
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Known hypersensitivity to recombinant human antibodies

Exclusion Criterion Unique to Arm B:

• Known significant hypersensitivity to paclitaxel or other drugs using the vehicle cremophor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: bevacizumab; Intravenous repeating dose; Drug: MNRP1685A; Escalating intravenous dose
Experimental: B	Drug: bevacizumab; Intravenous repeating dose; Drug: paclitaxel; Intravenous repeating dose; Drug: MNRP1685A; Escalating intravenous dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and nature of dose-limiting toxicities (DLTs)	Through study completion or early study discontinuation

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic (PK) parameters of MNRP1685A and bevacizumab, when appropriate, as data allow (total exposure, maximum and minimum serum concentration, clearance, and volume of distribution)	Through study completion or early study discontinuation

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: August 5, 2009
• First Submitted That Met QC Criteria: August 5, 2009
• First Posted (Estimate): August 7, 2009

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Solid Tumor; Avastin; Locally Advanced Solid Tumor
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab
• Other Study ID Numbers: ANP4667g