Safety of MP470 in Combination With Standard-of-Care Chemotherapy Regimens to Treat Solid Tumors (SGI-0470-02)

Safety and Dose Finding Study of Oral MP470, a Multi-targeted Tyrosine Kinase Inhibitor, in Combination With Standard-of-Care Chemotherapy Regimens

Adult subjects with malignant disease appropriate for treatment with carboplatin/paclitaxel, carboplatin/etoposide, topotecan, docetaxel or erlotinib according to the standard dosing regimen will be enrolled in each treatment arm.

Primary objective: Determine the MTD.

Secondary objectives: Response rates, PK, quantify MP-470 on PK of SOC, and collect pharmacodynamic information. Evaluate the overall safety of MP-470 when co-administered with specific SOC treatments.

Study Overview

• Status: Completed
• Conditions: Malignant Disease
• Intervention / Treatment: Drug: MP-470 + paclitaxel/carboplatin; Drug: MP-470 + carboplatin/etoposide; Drug: MP-470 + topotecan; Drug: MP-470 + docetaxel; Drug: MP-470 + erlotinib

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Premiere Oncology
  • California
    • Santa Monica, California, United States, 90404
      • Premiere Oncology
  • Texas
    • San Antonio, Texas, United States, 78229
      • CTRC at The UT Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • Audie Murphy Veterans Memorial Hospital (VA)
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapy (START)

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:

1. Malignant disease appropriate for initiating treatment with carboplatin/paclitaxel, carboplatin/etoposide, topotecan, docetaxel, or erlotinib.
2. Must be able to read, understand, and sign the IRB approved Informed Consent Form.
3. At least 18 years old.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Adequate bone marrow function; normal renal and hepatic function, normal cardiac function.

Exclusion Criteria:

1. Any other active invasive malignancy except non-melanoma skin cancers or cervical carcinoma in situ.
2. History of significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure and/or myocardial infarction.
3. Received any anticancer agent(s) within the past 3 weeks, including investigational agents, chemotherapy (6 weeks for nitrosoureas or mitomycin), immunotherapy, biologic or hormonal therapy other than LHRH agonists.
4. Received prior radiation therapy within the past 4 weeks.
5. Any serious, uncontrolled active infection that requires systemic treatment or known infection with HIV, HCV or HBV.
6. Patient requires treatment with immunosuppressive agents other than corticosteroids appropriate for the SOC chemotherapy regimen or those at stable doses for at least 2 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; oral MP-470 + paclitaxel/carboplatin	Drug: MP-470 + paclitaxel/carboplatin; Paclitaxel 200 mg/m2 IV infusion over 3 hours followed by carboplatin IV infusion over 1 hour to a target AUC of 6 mg∙min/mL on Day 1
EXPERIMENTAL: 2; oral MP-470 + carboplatin/etoposide	Drug: MP-470 + carboplatin/etoposide; Carboplatin IV infusion over 1 hour to target AUC of 5 mg min/mL on Day 1 followed by etoposide 100 mg/m2 IV infusion over 2 hours on Days 1-3
EXPERIMENTAL: 3; oral MP-470 + topotecan	Drug: MP-470 + topotecan; Topotecan 1.5 mg/m2 IV infusion over 30 minutes on Days 1-5
EXPERIMENTAL: 4; oral MP-470 + docetaxel	Drug: MP-470 + docetaxel; Docetaxel 75 mg/m2 IV infusion over 1 hour on Day 1
EXPERIMENTAL: 5; oral MP-470 + Erlotinib	Drug: MP-470 + erlotinib; 150 mg PO once daily at least 1 hour before or 2 hours after eating

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD)	March 2010

Secondary Outcome Measures

Outcome Measure	Time Frame
Response rate	March 2010
Pharmacokinetics, pharmacodynamic effects on biomarker modulation.	March 2010
Experience DLT	March 2010

Collaborators and Investigators

• Sponsor: Astex Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Anthony Tolcher, MD, The START Center for Cancer Care; Principal Investigator: Lee Rosen, MD, Premiere Oncology; Principal Investigator: Michael Gordon, MD, Premiere Oncology; Study Director: Greg Berk, MD, Astex Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Mita M, Gordon M, Rosen L, Kapoor N, Choy G, Redkar S, Taverna P, Oganesian A, Sahai A, Azab M, Bristow R, Tolcher AW. Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204. doi: 10.1007/s00280-014-2481-1. Epub 2014 May 22.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (ACTUAL): December 1, 2009
• Study Completion (ACTUAL): December 1, 2009

Study Registration Dates

• First Submitted: April 13, 2009
• First Submitted That Met QC Criteria: April 14, 2009
• First Posted (ESTIMATE): April 15, 2009

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Malignant disease; MP-470; Multi-targeted Tyrosine Kinase Inhibitor
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Topoisomerase I Inhibitors; Docetaxel; Carboplatin; Etoposide; Paclitaxel; Erlotinib Hydrochloride; Topotecan
• Other Study ID Numbers: SGI-0470-02