Dose Escalation of Velcade Daily Dose in Patients With Solid Tumors

NCT02220049 | Completed Phase 1

• 2 other identifiers: 2009-014354-152009/1520
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

VELCADE has demonstrated marked activity in haematological cancers leading to registration (MM, MCL). Currently only biweekly or weekly regimens have been explored. Key signalling pathways which are aberrant in haematological cancers are also present in solid tumors. VELCADE covers a broad spectrum of proteins, which are pivotal in carcinogenesis.VELCADE as a single agent \& in combination with chemotherapy in solid cancers has shown modest and real anti-tumor activity but insufficient for Phase III development. VELCADE PK exposure may be inadequate in solid tumors compared to "liquid cancers." VELCADE daily low dose administration may allow a greater PK exposure to be achieved, which is tolerated Hypotheses: VELCADE daily dosing (5-days on, 2-days off) is tolerable at biologically active doses VELCADE daily dosing (5-days on, 2-days off) results in increased PK (AUC)/PD (20S proteasome inhibition) VELCADE daily dosing (5-days on, 2-days off) with increased PK/PD results in improved anti-tumor activity (Increased tolerable VELCADE AUC may potentially cross the threshold required for clinically significant anti-tumor activity in solid cancers). Some preclinical data suggest that: VELCADE daily dosing results in increased proteasome inhibition in tumor tissues Combination of VELCADE + XRT/other daily dosing agent may have increased anti-tumor activity compared to monotherapy alone.

Conditions

Advanced or Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Identify maximum tolerated dose

  Assessed every week from inclusion during the first 28 days and then every 28 days up to 19 months

Secondary Outcomes (1)

• Efficacy

  Assessed within 7 days of every cycle (28 days) up to 19 months

Study Arms (1)

Velcade

EXPERIMENTAL

Dose level Dose(mg/m²) d1-5, d8-12, d15-19 Cohort -2 Velcade 0.3 mg/m² Cohort -1 Velcade 0.4 mg/m² Cohort 1 Velcade 0.5 mg/m² Cohort 2 Velcade 0.6 mg/m² Cohort 3 Velcade 0.7 mg/m² Cohort 4 Velcade 0.8 mg/m² Cohort 5 Velcade 0.9 mg/m² Cohort 6 Velcade 1.0 mg/m² Cohort 7 Velcade 1.1 mg/m²

Drug: Bortezomib

Interventions

Bortezomib DRUG

Also known as: VELCADE

Velcade

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Target population
• Subjects with advanced or metastatic solid tumors for whom the standard of care is ineffective or inappropriate
• Ability to comply with visits/procedures required by the protocol
• Life expectancy of at least 3 months
• ECOG performance status score 0-1
• Subjects with Histologic or cytologic diagnosis of any solid tumor (nonhematologic malignancy).
• A tumor paraffin tissue block or 20-30 unstained slides from the tumor tissue block or enough slides from an FNA to allow for biomarker and predictive marker analyses. (This biopsy need not be obtained fresh at the time of screening. Obtaining unstained slides from the original diagnostic biopsy will suffice to meet this requirement).
• Measurable or evaluable disease
• Prior anti-cancer treatments are permitted (i.e. chemotherapy, radiotherapy, hormonal, or immunotherapy) with the following exceptions:

You may not qualify if:

• At least 3 weeks must have elapsed since the last chemo-therapy, immunotherapy or radiotherapy and the beginning of protocol therapy. At least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin.
• At least 3 weeks must have elapsed since the last anti-cancer hormonal therapy or antibody targeted therapy (e.g. Bevacizumab, Cetuximab, Trastuzumab). Hormonal treatment by analog LHRH will be allowed for patients with prostate cancer For extended-release formulations, the washout period must extend 1 month beyond the duration of activity of the formulation (e.g., 3 months for the activity of a depot formulation + 1 month wash out).
• Age and Sex
• men and women 18 - 75
• Male and female patients of childbearing potential must use effective contraceptive measures during the study an d for at least 3 months after the end of the study treatment
• Sex and Reproductive Status
• Male and female patients of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to three months after the study.
• Male and female patients of childbearing potential using a prohibited contraceptive method.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to study drug administration.
• Subjects who have documented unstable or untreated brain metastasis for at least 4 weeks and who are still requiring steroids (Subjects with treated and stably controlled CNS metastases for at least 4 weeks and are no longer on steroids are eligible for this study).
• Medical History and Concurrent Diseases
• A serious uncontrolled medical disorder or active infection, which would impair the ability of the subject to receive protocol therapy
• History of thromboembolic disease or bleeding diatheses within the last six (6) months. This includes those subjects with tumors that were known to have spontaneously bled in the past.
• History or presence of the diffuse interstitial lung disease or pericardial disease

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val de Marne, 94805, France

Location

MeSH Terms

Interventions

Bortezomib

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Rastislav BAHLEDA, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2014
• First Posted: August 19, 2014
• Study Start: December 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: March 25, 2016

Record last verified: 2016-03

Locations

FR (1)