A Study of BEZ235 in Adult Japanese Patients With Advanced Solid Tumors

A Phase I Study of BEZ235, Administered Orally in Adult Japanese Patients With Advanced Solid Tumors

In this study, BEZ235 will be administered to adult patients with advanced solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. The trial will confirmed the safety and tolerability and determine the MTD of BEZ235 in Japanese patients.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: BEZ235

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Hyogo
    • Kobe-city, Hyogo, Japan, 650-0017
      • Novartis Investigative Site
  • Oita
    • Yufu, Oita, Japan, 879-5593
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with histologically-confirmed, advanced unresectable solid tumors who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists.
2. At least one measurable lesion as defined by RECIST criteria for solid tumors.
3. Age ≥ 20
4. Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2
5. Life expectancy of ≥ 12 weeks
6. Patients must have the laboratory values Patients in the expansion part of this study have to meet the following criteria in addition to the criteria described above.
7. Availability of a representative tumor tissue specimen (either archival tumor or fresh tumor biopsy) for pre-screening.
8. Patients whose molecular status proved to meet the criteria (PIK3CA mutation/amplification and/or PTEN mutation and/or low/null PTEN expression) during pre-screening.

Exclusion Criteria:

1. Patients who have brain metastases or who have signs/symptoms attributable and have not been assessed with radiologic imaging to rule out the presence of brain metastases
2. Patients with any peripheral neuropathy ≥ CTCAE grade 2
3. Patients with unresolved diarrhea ≥ CTCAE grade 2
4. Patients with a history of photosensitivity reactions to other drugs
5. Women of child-bearing potential who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial in both sexes. Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least consecutive 1 years (i.e., who has had menses any time in the preceding consecutive 2 years), must have a negative serum pregnancy test ≤ 7 days prior to starting BEZ235.

Other protocol-defined inclusion/exclusion criteria may apply

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BEZ235 Dose Escalation once daily; oral BEZ235 once daily (q.d.)	Drug: BEZ235
Experimental: BEZ Dose escalation twice daily; oral BEZ235 twice daily (b.i.d.)	Drug: BEZ235

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To establish Maximum tolerate dose (MTD)	Every week

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety assessed by type, frequency and severity of adverse events	Every week
Efficacy assessed by RECIST	Every 2 months
To characterize the PK profiles	Every 2 weeks
To assess the biomarkers	Every 2 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Toyoda M, Watanabe K, Amagasaki T, Natsume K, Takeuchi H, Quadt C, Shirao K, Minami H. A phase I study of single-agent BEZ235 special delivery system sachet in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2019 Feb;83(2):289-299. doi: 10.1007/s00280-018-3725-2. Epub 2018 Nov 16.

Helpful Links

• Results for CBEZ235A1101 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: September 2, 2010
• First Submitted That Met QC Criteria: September 3, 2010
• First Posted (Estimate): September 6, 2010

Study Record Updates

• Last Update Posted (Actual): December 9, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: mTOR; PI3K; Advanced solid tumor
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Dactolisib
• Other Study ID Numbers: CBEZ235A1101