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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Cancers

Intervention / Treatment
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* Drug: bevacizumab
* Drug: MNRP1685A
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: MNRP1685A<br>* Escalating intravenous dose<br>|
| Experimental: B<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: MNRP1685A<br>* Escalating intravenous dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor, Locally Advanced Solid Tumor, Avastin