Clinical trial NCT00954642: A Study of MNRP1685A in Combination With Bevacizumab With or Without Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Cancers
Keywords: Solid Tumor
Locally Advanced Solid Tumor
Avastin
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2009-08-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and nature of dose-limiting toxicities (DLTs)
timeFrame: Through study completion or early study discontinuation
Secondary outcomes:
measure: Pharmacokinetic (PK) parameters of MNRP1685A and bevacizumab, when appropriate, as data allow (total exposure, maximum and minimum serum concentration, clearance, and volume of distribution)
timeFrame: Through study completion or early study discontinuation
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Rainer Brachmann, M.D.
role: STUDY_DIRECTOR
References: