Phase Ib/II Trial of BEZ235 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer
This study is currently recruiting participants.
Verified May 2013 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01495247
First received: September 30, 2011
Last updated: May 16, 2013
Last verified: May 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
This is a prospective, multi-center, open-label, phase Ib/ II study (two parts) with patients that have locally advanced or metastatic HER2 negative breast cancer. The first part (phase Ib) will investigate the MTD / Recommended Phase 2 Dose (RP2D) of the combination therapy of BEZ235 twice daily (b.i.d.) and weekly paclitaxel using a Bayesian model. When MTD/ RP2D is established the second part (phase II) will start. Phase II will evaluate the efficacy and the safety of weekly paclitaxel alone compared to weekly paclitaxel plus BEZ235 bid.
| Condition | Intervention | Phase |
|---|---|---|
|
Inoperable Locally Advanced Breast Cancer Metastatic Breast Cancer (MBC) |
Drug: BEZ235 + Paclitaxel |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Dose-finding Phase Ib Study Followed by an Open-label, Randomized Phase II Study of BEZ235 Plus Paclitaxel in Patients With HER2 Negative, Inoperable Locally Advanced or Metastatic Breast Cancer |
Resource links provided by NLM:
Genetics Home Reference related topics:
breast cancer
Drug Information available for:
Paclitaxel
U.S. FDA Resources
Further study details as provided by Novartis:
Primary Outcome Measures:
- Phase lb: Dose Limiting Toxicities (DLTs) the first cycle of treatment [ Time Frame: At first treatment intake (Cycle 1 Day 1 = C1D1), C1D8, C1D15, C1D22 and C2D1 [a cycle = 4 weeks = 28 days] ] [ Designated as safety issue: Yes ]
DLT is defined as treatment-related toxicity (classified according Common Toxicity Criteria for Adverse Events (CTCAE) Version 4) occurring during the first 28 treatment days and meeting specific protocol-predefined criteria.
The information will be integrated in a Bayesian logistic regression model with overdose control to estimate the maximum tolerated dose (MTD).
Secondary Outcome Measures:
- Phase lb: Frequency and severity of adverse events [ Time Frame: At screening, every week (C1D1, C1D8, C1D15, C1D22, C2D1, C2D8, etc.) until 30-45 days after treatment discontinuation [estimated time frame: 18 months]. ] [ Designated as safety issue: Yes ]Incidence of adverse events (based on CTCAE Version 4) summarized by system organ class and/or preferred term, severity and relation to study treatment.
- Phase lb: Progression free survival (PFS) [ Time Frame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) until disease progression or death for any cause [estimated time frame: 18 months]. ] [ Designated as safety issue: No ]PFS is defined as the time from start of treatment to objective tumor progression or death from any cause. Radiological assessments will be performed every 8 weeks.
- Phase lb: Overall Response Rate (ORR) [ Time Frame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) during the study [estimated time frame: 18 months]. ] [ Designated as safety issue: No ]Proportion of patients with a best overall response of CR or PR according to RECIST 1.1
- Phase lb: Clinical Benefit Rate (CBR) [ Time Frame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) during the study [estimated time frame: 18 months]. ] [ Designated as safety issue: No ]Proportion of patients with a best overall response of CR, PR or SD with a duration of 24 weeks or longer according to RECIST 1.1
| Estimated Enrollment: | 230 |
| Study Start Date: | January 2012 |
| Estimated Study Completion Date: | April 2015 |
| Estimated Primary Completion Date: | January 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: BEZ235 + paclitaxel (phase lb)
Increasing doses of oral BEZ235 administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment will be organized into cycles of 28 days.
|
Drug: BEZ235 + Paclitaxel
Doses of oral BEZ235 (BID), supplied as 200mg, 300mg or 400mg in SDS sachets, together with standard weekly paclitaxel at a fixed dose (80mg/m²) during 1h by i.v. in infusion. The paclitaxel infusion will be given in the morning and directly thereafter the BEZ235 dose will be given. BEZ235 doses will be escalated in cohorts of 3 to 6 patients guided by an adaptive Bayesian logistic regression model with overdose control until MTD/RP2D has been established. The initial dose level for the first cohort will be 200mg (BID), and then based on the Bayesian model the dose may be escalated to 300mg, 400mg, 500mg or 600mg for the next cohorts. |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria (phase lb):
- Females with Breast cancer that is histologically or cytologically confirmed, HER2 negative and locally advanced or metastatic as confirmed by radiology
- ECOG performance status 0 and 1
- Adequate bone marrow and organ function
Exclusion Criteria (Phase lb):
- Previous treatment with PI3K and/or mTOR inhibitors
- Symptomatic Central Nervous System (CNS) metastases
- Concurrent malignancy or malignancy in the last 5 years prior to start of study treatment
- Wide field radiotherapy ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug
- Active cardiac disease (e.g. LVEF less than institutional lower limit of normal, QTcF > 480 msec, unstable angina pectoris, ventricular, supraventricular or nodal arrhythmias)
- Inadequately controlled hypertension
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BEZ235 and/or paclitaxel
- Treatment at start of study treatment with drugs with a known risk to induce Torsades de Pointes, moderate and strong inhibitors or inducers of isoenzyme CYP3A4, warfarin and coumadin analogues, LHRH agonists
- Sensitivity to paclitaxel treatment
- Uncontrolled diabetes mellitus
- Pregnant or nursing (lactating) woman
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01495247
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | |
| Contact: Novartis Pharmaceuticals |
Locations
| United States, Arizona | |
| Ironwood Cancer and Research Centers Ironwood | Not yet recruiting |
| Chandler, Arizona, United States, 85224 | |
| Contact: Ann Kolb AKolb@ironwoodcrc.com | |
| Principal Investigator: Mikhail Shtivelband | |
| United States, Arkansas | |
| Highlands Oncology Group | Not yet recruiting |
| Fayetteville, Arkansas, United States, 72703 | |
| Contact: Vicki Weaver +1 479 587 1700 vweaver@hogonc.com | |
| Principal Investigator: Joseph Thaddeus Beck | |
| United States, Texas | |
| Texas Oncology, P.A. Dept.ofTexas Oncology, PA | Not yet recruiting |
| Dallas, Texas, United States, 75246 | |
| Contact: Stephanie Preston +1 214 370 1000 stephanie.preston@usoncology.com | |
| Principal Investigator: Carlos Roberto Becerra | |
| US Oncology Central Monitoring | Withdrawn |
| Dallas, Texas, United States, 75246 | |
| Brazil | |
| Novartis Investigative Site | Not yet recruiting |
| Rio de Janeiro, RJ, Brazil, 20230-130 | |
| Novartis Investigative Site | Not yet recruiting |
| Porto Alegre, RS, Brazil, 90035-903 | |
| Novartis Investigative Site | Not yet recruiting |
| Porto Alegre, RS, Brazil, 90610-000 | |
| Novartis Investigative Site | Not yet recruiting |
| Barretos, SP, Brazil, 14784-400 | |
| Novartis Investigative Site | Not yet recruiting |
| São Paulo, SP, Brazil, 01246-000 | |
| France | |
| Novartis Investigative Site | Recruiting |
| Dijon Cedex, France, 21034 | |
| Novartis Investigative Site | Recruiting |
| Saint-Herblain Cédex, France, 44805 | |
| Spain | |
| Novartis Investigative Site | Active, not recruiting |
| Hospitalet de LLobregat, Catalunya, Spain, 08907 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01495247 History of Changes |
| Other Study ID Numbers: | CBEZ235B2101, 2011-002400-32 |
| Study First Received: | September 30, 2011 |
| Last Updated: | May 16, 2013 |
| Health Authority: | United States: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Australia: Department of Health and Ageing Therapeutic Goods Administration Brazil: National Health Surveillance Agency Belgium: Federal Agency for Medicinal Products and Health Products France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Hong Kong: Department of Health Italy: National Institute of Health Korea: Food and Drug Administration Russia: Ministry of Health of the Russian Federation Singapore: Health Sciences Authority Spain: Spanish Agency of Medicines Taiwan: Department of Health Thailand: Food and Drug Administration Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Novartis:
|
Locally advanced metastatic breast cancer HER2 negative |
PI3K pathway paclitaxel mTOR inhibitor |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Tubulin Modulators |
Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013