Gemcitabine and Dasatinib in Advanced Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00429234
First received: January 29, 2007
Last updated: April 1, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Advanced Cancer
Solid Tumors
Drug: Dasatinib
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Open-Labeled Trial of Gemcitabine and Dasatinib in Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated combination doses (MTD) [ Time Frame: 8 week cycle for Cycle 1, all other cycles 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 54
Study Start Date: January 2007
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib + Gemcitabine
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
Starting dose 70 mg by mouth daily for Week 1. Cycle is 28 days, except Cycle 1 which is 8 weeks.
Other Names:
  • BMS-354825
  • Sprycel
Drug: 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.
Other Names:
  • Gemzar
  • Gemcitabine Hydrochloride

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent
  2. Available for protocol-required follow-up
  3. Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 1
  4. Histologic or cytologic diagnosis of a primary solid malignancy
  5. Evidence (radiographic or tissue confirmation) that the disease is metastatic, or locally advanced in patients who are not candidates for standard therapy
  6. Measurable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST)
  7. 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
  8. 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
  9. Adequate renal function defined as serum creatinine </= 1.5 times the institutional ULN
  10. 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
  11. 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)
  12. Men and women, ages 18 and older
  13. 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
  14. Continued from inclusion #13: WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >/= 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL]
  15. Continued from inclusion #13 and 14: Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
  16. 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
  17. At the MTD expansion phase of the protocol, all patients must have fine needle aspirate (FNA) biopsiable disease

Exclusion Criteria:

  1. 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
  2. Women who are pregnant or breastfeeding
  3. Women with a positive pregnancy test on enrollment or prior to study drug administration
  4. 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
  5. Received extensive prior radiation therapy to the bone marrow. Generally, patients should have radiation to </= 25% of bone marrow-containing skeleton
  6. 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)
  7. A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive protocol therapy
  8. 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,
  9. Continued from exclusion #9: g) any history of second or third degree heart block (may be eligible if currently have a pacemaker) h) heart rate < 50 / minute on pre-entry electrocardiogram or i) uncontrolled hypertension
  10. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
  11. 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
  12. Patients who have not recovered from adverse events greater than grade 1 due to agents administered more than 4 weeks earlier
  13. Prior exposure to dasatinib
  14. 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
  15. 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
  16. 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
  17. Social situations that would limit compliance with study requirements
  18. History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, dasatinib, or other agents used in this study
  19. Any pleural effusion felt to be clinically significant by the attending physician or principal investigator (P.I.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00429234

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: David S. Hong, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00429234     History of Changes
Other Study ID Numbers: 2006-0574
Study First Received: January 29, 2007
Last Updated: April 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancer
Solid Tumors
Dasatinib
BMS-354825
Sprycel
Gemcitabine
Gemcitabine Hydrochloride
Gemzar

Additional relevant MeSH terms:
Neoplasms
Gemcitabine
Dasatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014