Study of Erlotinib in Combination With Bortezomib

NCT00895687 | Completed Phase 1

• 2 other identifiers: 2008-0554NCI-2012-01631
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of Tarceva (erlotinib hydrochloride) that can safely be given in combination with Velcade (bortezomib). The safety of this drug combination will also be studied.

Conditions

Advanced Cancer

Keywords

Metastatic Cancer; Bortezomib; Velcade; Erlotinib; Erlotinib Hydrochloride; Tarceva; EGFR; EGFR mutations

Outcome Measures

Primary Outcomes (2)

• Tumor Response

  Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a \>/= 25% decrease in cancer antigen 125 (CA125) for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e. decrease in size by 10% or more, or a decrease in the tumor density, as measured in Hounsfield units (HU), by more than or equal to 15%.

  Evaluation of response after two 21-day cycles of treatment

• Maximum Tolerated Dose (MTD)

  MTD defined as highest dose studied in which incidence of dose limiting toxicity (DLT) was less than 33%. DLT defined as any Grade 3 or 4 non-hematologic toxicity defined in the NCI CTC v3.0, even if expected and believed related to study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by the NCI-CTCAE), despite supportive care; any Grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE that is attributable to the therapy.

  21 days

Study Arms (1)

Erlotinib + Bortezomib

EXPERIMENTAL

Up to 4 dose levels of study drug combination tested with 3-6 participants enrolled at each dose level. Erlotinib beginning dose of 150 mg taken by mouth daily for 21-day cycle. Bortezomib beginning dose of 1. mg/m\^2 by vein over about 1-5 minutes on Days 1, 4, 8, and 11 of each 21-day cycle.

Drug: Erlotinib Hydrochloride; Drug: Bortezomib

Interventions

Erlotinib Hydrochloride DRUG

Beginning dose of 150 mg taken by mouth daily for 21-day cycle.

Also known as: Erlotinib, Tarceva

Erlotinib + Bortezomib

Bortezomib DRUG

Beginning dose of 1. mg/m\^2 by vein over about 1-5 minutes on Days 1, 4, 8, and 11 of each 21-day cycle.

Also known as: Velcade, LDP-341, MLN341, PS-341

Erlotinib + Bortezomib

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have had no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
• Measurable or non-measurable disease.
• Patients must be \>/= 6 wks beyond treatment with a nitrosourea or mitomycin-C, \>/= 4 wks beyond other chemotherapy or external beam radiation therapy (XRT), and must have recovered to \</= Grade 1 toxicity for any treatment-limiting toxicity resulting from prior therapy. (Exception: patients may have received palliative low dose XRT one week before treatment provided it is not given to the only targeted lesions).
• (continued from above) Also, patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 wks, whichever is shorter, from the last day of treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 2 (Karnofsky \>/= 60%)
• Patients must have normal organ and marrow function defined as: absolute neutrophil count \>/=1,000/mL; platelets \>/=50,000/mL; creatinine \</= 2 X upper limit of normal (ULN); total bilirubin \</= 2.0; ALT(SGPT) \</= 3 X ULN; Exception for patients with liver metastasis: total bilirubin \</= 3 x ULN; ALT(SGPT) \</= 5 X ULN.
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
• Ability to understand and the willingness to sign a written informed consent document
• For the MTD expansion cohort, patients will be eligible if they meet one of the following criteria: (I) Have an EGFR-sensitive mutation and have been previously treated with EGFR inhibitor therapy but have subsequently developed resistance, OR (II) Have an EGFR-resistant mutation, OR (III) Do not have an EGFR mutation, but have benefited from EGFR inhibitor therapy (including either \>/=4 months of stable disease \[SD\] OR a \>/= partial response \[PR\]).

You may not qualify if:

• Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection; altered mental status or psychiatric illness/social situations that would limit compliance with study requirements and/or obscure study results.
• Uncontrolled systemic vascular hypertension (systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg on medication).
• Patients with clinically significant cardiovascular disease: history of cardiovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
• Patients with colorectal carcinoma with tumors that demonstrate a Kirsten rat sarcoma (KRAS) mutation.
• Pregnant or lactating women.
• Patients with a history of bone marrow transplant within the previous two years.
• Patients with a known hypersensitivity to any of the components of the drug products.
• Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.
• Patients with major surgery within 30 days prior to entering the study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Erlotinib Hydrochloride; Bortezomib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jennifer J. Wheler, MD

  M.D. Anderson Cancer Center

  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: May 6, 2009
• First Posted: May 8, 2009
• Study Start: April 1, 2009
• Primary Completion: July 1, 2015
• Last Updated: July 13, 2015

Record last verified: 2015-07

Locations

US (1)