Gemcitabine and Dasatinib in Advanced Solid Tumors

NCT00429234 | Completed Phase 1

• 1 other identifier: 2006-0574
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of dasatinib in combination with gemcitabine that can be given to patients with advanced solid tumors. The safety of this combination of study drugs will also be studied. Researchers also want to study the pharmacodynamics (PDs) of this study drug combination. PD testing is used to learn what effect the drugs have on your tumors.

Conditions

Advanced Cancer; Solid Tumors

Keywords

Advanced Cancer; Solid Tumors; Dasatinib; BMS-354825; Sprycel; Gemcitabine; Gemcitabine Hydrochloride; Gemzar

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated combination doses (MTD)

  8 week cycle for Cycle 1, all other cycles 28 days

Study Arms (1)

Dasatinib + Gemcitabine

EXPERIMENTAL

Dasatinib starting dose 70 mg by mouth daily for Week 1. Cycle is 28 days, except Cycle 1 which is 8 weeks. Gemcitabine starting dose of 800 mg/m\^2 by vein once weekly over 30 minutes beginning Cycle 1 Day 1. All other cycles once weekly for 7 weeks on Days 8, 15, 22, 29, 36, and 43. Cycle is 28 days, except Cycle 1 which is 8 weeks.

Drug: Dasatinib; Drug: Gemcitabine

Interventions

Dasatinib DRUG

Starting dose 70 mg by mouth daily for Week 1. Cycle is 28 days, except Cycle 1 which is 8 weeks.

Also known as: BMS-354825, Sprycel

Dasatinib + Gemcitabine

Gemcitabine DRUG

Starting dose of 800 mg/m\^2 by vein once weekly over 30 minutes beginning Cycle 1 Day 1. All other cycles once weekly for 7 weeks on Days 8, 15, 22, 29, 36, and 43. Cycle is 28 days, except Cycle 1 which is 8 weeks.

Also known as: Gemzar, Gemcitabine Hydrochloride

Dasatinib + Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Available for protocol-required follow-up
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 1
• Histologic or cytologic diagnosis of a primary solid malignancy
• Evidence (radiographic or tissue confirmation) that the disease is metastatic, or locally advanced in patients who are not candidates for standard therapy
• Measurable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST)
• Adequate bone marrow function defined as: a) absolute neutrophil count (neutrophil and bands) \>/= 1,500 cells/mm\^3, b) platelet count \>/= 100,000 cells/mm\^3, c) hemoglobin \>/= 9.0 g/dl
• Adequate hepatic function defined as: a) total bilirubin \</= 1.5 times the institutional upper limit upper limit of normal (ULN), b) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \</= 2.0 times the institutional ULN, c) Exception: patients with primary liver tumors or known liver metastases: \</= 3.0 times the institutional ULN for total bilirubin, AST and ALT
• Adequate renal function defined as serum creatinine \</= 1.5 times the institutional ULN
• Serum potassium and magnesium levels within institutional normal limits. Total serum calcium or ionized calcium level must be greater than or equal to the lower limit of normal. Patients with low potassium, calcium and magnesium levels may be repleted to allow for protocol entry
• Prior chemo-, radio-, hormonal or immunotherapy are allowed. Patients must have recovered from toxicity due to prior therapy i.e., toxicity has resolved to baseline or is deemed irreversible. At least 4 weeks must have elapsed since the last chemotherapy or investigational agent (6 weeks for nitrosoureas, mitomycin-C, and liposomal doxorubicin), immunotherapy or radiotherapy and the beginning of protocol therapy. At least 2 weeks must have elapsed since last hormonal therapy or exposure to any other "targeted" kinase inhibitor (e.g., imatinib mesylate)
• Men and women, ages 18 and older
• Women of childbearing potential (WOCBP) must be using an adequate method (i.e. barrier, spermicidal) of contraception to avoid pregnancy throughout the study and for a period of at least 1 month prior and at least 3 months after the study in such a manner that the risk of pregnancy is minimized
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication
• At the MTD expansion phase of the protocol, all patients must have fine needle aspirate (FNA) biopsiable disease

You may not qualify if:

• Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method (i.e. barrier, or spermicidal) to avoid pregnancy for the entire study period including the period from one month prior to starting study medication and for a period of at least 3 months after the study
• Women who are pregnant or breastfeeding
• Women with a positive pregnancy test on enrollment or prior to study drug administration
• Men who are unwilling or unable to use an acceptable method (i.e. barrier, or spermicidal) of birth control for the entire study period and for at least 3 months after completion of study medication if their sexual partners are WOCBP
• Received extensive prior radiation therapy to the bone marrow. Generally, patients should have radiation to \</= 25% of bone marrow-containing skeleton
• Symptomatic brain metastasis that are either untreated or uncontrolled by surgery and or radiotherapy. Patients with symptoms of brain metastasis are not eligible unless brain metastasis are ruled out by CT or MRI and/or fully treated surgically or with whole-brain radiotherapy (WBRT)
• A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive protocol therapy
• Uncontrolled or significant cardiovascular disease, including: a)A myocardial infarction within 6 months, b)Subjects with known symptomatic cardiomyopathy, c)Uncontrolled angina within 3 months, d)Congestive heart failure within 3 months, e)diagnosed or suspected congenital long QT syndrome, f)any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes). Prolonged QTc interval on pre-entry electrocardiogram (\>450 msec). If the automated reading is prolonged (i.e.\>450 msec), the ECG should be manually overread,
• Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
• History of significant bleeding disorder including: a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), c) Documented major bleeding episode from the GI tract within 6 months, d) Vasculitis, e) Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy
• Patients who have not recovered from adverse events greater than grade 1 due to agents administered more than 4 weeks earlier
• Prior exposure to dasatinib
• Gastric pH modifying agents. Subjects should not take proton pump inhibitors and H2 antagonists. Short-acting antacid agents may be taken, and replaced for patients who are on gastric pH modifying agents prior to enrollment
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
• Because patients with immune deficiency are at increased risk of lethal infections when treated with myelosuppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with dasatinib or other agents administered during the study

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Interventions

Dasatinib; Gemcitabine

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides

Study Officials

• David S. Hong, 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: January 29, 2007
• First Posted: January 31, 2007
• Study Start: January 1, 2007
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: April 4, 2013

Record last verified: 2013-04

Locations

US (1)