Sorafenib and Bevacizumab in Combination With Paclitaxel in Patients With Solid Tumors

Phase I Dose-Escalation Drug-Interaction Study of Sorafenib and Bevacizumab in Combination With Paclitaxel in Patients With Solid Tumors

The purpose of this study is to evaluate the safety and tolerability and describe the maximum tolerated dose (MTD) of treatment with escalating doses of sorafenib in combination with bevacizumab and paclitaxel for patients with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: SOLID TUMORS
• Intervention / Treatment: Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center

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:

• Histological or cytological diagnosis of a solid tumor with evidence of residual, recurrent, or metastatic disease. Patients must be incurable by surgical or other standard available therapy
• Measurable or evaluable disease; tumor size of ≥ 2 cm on CT scan
• Patients may have received prior standard taxane therapy or anti-VEGF therapy, but may not have progressed on both therapies. Progression on one type therapy (either taxane or anti-VEGF) is allowed

Exclusion Criteria:

• History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis).
• Prior chemotherapy ≤ 3 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
• Prior biologic or immunotherapy ≤ 3 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
• Prior full pelvic field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization. Patients must have recovered to less than or equal to grade 1 from all therapy-related toxicities except alopecia. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of evaluable disease
• Major surgery (i.e., laparotomy) ≤ 4 weeks prior to randomization or anticipation of need for major surgical procedure during the course of the study
• Minor surgery ≤ 2 weeks prior to randomization. Insertion of a vascular access device is not considered major or minor surgery in this regard. Patients must have recovered from all surgery-related toxicities
• Peripheral neuropathy with functional impairment ≥ Common Terminology Criteria (CTC) grade 2 neuropathy, regardless of causality
• Pleural effusion or ascites that causes respiratory compromise (≥ CTC grade 2 dyspnea)
• Concurrent severe and/or uncontrolled cardiac, vascular or infectious conditions (as described in the protocol) which could compromise participation in the study
• Patients at risk of QT prolongation such as patients with congenital long QT syndrome or with long corrected QT (QTc) at baseline (i.e. QTc greater than 450 msec in males, and greater than 470 msec in females) will be excluded
• Lung carcinoma of squamous cell histology (mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is not acceptable).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib, Bevacizumab & Paclitaxel; Paclitaxel is given as i.v infusion over 60 min on days 1, 8, 15 every 28 days. Sorafenib is given orally starting with cycle 1 day 2. Bevacizumab is given as i.v infusion on days 1 and 15 every 28 days.	Drug: Sorafenib; Cohort 1 200 mg po BID D1-5; Cohort 2 200 mg po BID; Cohort 3 400 mg po BID D1-5 Cohort 4 400 mg po BID; Other Names: Bay 43-9006

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and tolerability and describe the maximum tolerated dose (MTD) of treatment with escalating doses of sorafenib in combination with bevacizumab and paclitaxel for patients with advanced solid tumors.	baseline through end of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the pharmacokinetics of paclitaxel and sorafenib alone and in combination	baseline through end of treatment
To evaluate pharmacodynamic changes a)in tumor vascular parameters and b)in plasma VEGF and soluble VEGF receptor levels, and correlate with clinical outcomes and sorafenib pharmacokinetic (PK) profile.	baseline through end of treatment
To evaluate variants in genes of paclitaxel drug-metabolism and drug-transporters P glycoprotein and correlate with PK profile for paclitaxel and with clinical outcomes	baseline through end of treatment

Collaborators and Investigators

• Sponsor: Safi Shahda
• Collaborators: Bayer; Genentech, Inc.
• Investigators: Principal Investigator: Safi G Shahda, MD, Indiana University School of Medicine

Publications and helpful links

General Publications

• Chiorean EG, Perkins SM, Strother RM, Younger A, Funke JM, Shahda SG, Hahn NM, Sandrasegaran K, Jones DR, Skaar TC, Schneider BP, Sweeney CJ, Matei DE. Phase I, Pharmacogenomic, Drug Interaction Study of Sorafenib and Bevacizumab in Combination with Paclitaxel in Patients with Advanced Refractory Solid Tumors. Mol Cancer Ther. 2020 Oct;19(10):2155-2162. doi: 10.1158/1535-7163.MCT-20-0277. Epub 2020 Aug 26.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2008
• Primary Completion (Actual): January 4, 2011
• Study Completion (Actual): September 14, 2014

Study Registration Dates

• First Submitted: December 10, 2007
• First Submitted That Met QC Criteria: December 10, 2007
• First Posted (Estimate): December 12, 2007

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: September 21, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: solid tumor
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 0706-05 IUCRO-0171