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Phase I Open-Labeled Trial of Gemcitabine and Dasatinib in Advanced Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Advanced Cancer, Solid Tumors

Thank you

Trial Information

Phase I Open-Labeled Trial of Gemcitabine and Dasatinib in Advanced Solid Tumors


Dasatinib is designed to block several proteins that have been shown to be important for the
growth, spreading, and survival of cancers cells.

Gemcitabine is designed to disrupt the growth of cancer cells, which may cause them to die
and prevent further growth of cancer cells.

The amount of dasatinib and gemcitabine that you receive will depend on when you start on
this study. There will be 3 participants enrolled in each group. The first group of
participants enrolled on this study will be given small doses of dasatinib and gemcitabine.
If no intolerable side effects are experienced, the next group of participants will be
enrolled at a higher dose level. This process will continue until researchers find the
highest tolerable dose of dasatinib and gemcitabine that can be given without intolerable
side effects occurring. Up to 15 more patients will be enrolled at this highest tolerable
dose in an expansion group. If you are enrolled in the expansion group, you will have a
biopsy for PD testing prior to your first day on the study. Your doctor will tell you which
group you are enrolled in.

Your study doctor will tell you what dose of dasatinib and gemcitabine you will be receiving
and how it compares to the doses other participants have received. While on study, your dose
may be increased to the next higher level, if the next higher dose level has already been
tested in other participants and found to be tolerable.

You will take dasatinib by mouth once a day for 7 days in a row before you begin receiving
gemcitabine by vein. If no intolerable side effects from dasatinib occur, you will continue
taking it for the rest of the study. If you are enrolled in an expansion group, you will
take dasatinib by mouth once a day for 56 days in a row.

If the disease get worse or you experience any intolerable side effects with dasatinib, you
will be taken off this study before you begin taking gemcitabine.

You will receive gemcitabine by vein over 30 minutes starting on Day 8. The first cycle is
9 weeks long (63 days). You will receive gemcitabine by vein over 30 minutes once a week for
7 weeks on Days 8, 15, 22, 29, 36, 43, and 50. On Days 51-63, you will not receive any
gemcitabine (a rest period for this drug), but you will continue to take dasatinib once a
day. There will not be a rest period for dasatinib.

If you are enrolled in an expansion group, you will receive gemcitabine by vein over 30
minutes starting on Day 1. The first cycle is 8 weeks long (56 days). You will receive
gemcitabine by vein over 30 minutes once a week for 7 weeks on Days 1, 8, 15, 22, 29, 36 and
43. On Days 44- 56, you will not receive any gemcitabine (a rest period for this drug), but
you will continue to take dasatinib once a day. There will not be a rest period for
dasatinib.

Cycle 2 and all other cycles will equal 28 days. You will continue to take dasatinib once a
day. You will receive gemcitabine once a week for 3 weeks on Days 1, 8, and 15. On Days
16-28, you will not receive any gemcitabine, but you will continue to take dasatinib once a
day.

If you experience any intolerable side effects, you may need to have additional blood drawn
(about 2 teaspoons) to monitor your condition. Your dose level may be reduced to stop
intolerable side effects from occurring, depending on what the study doctor thinks is best.
If the disease gets worse or you continue to experience any intolerable side effects with
gemcitabine, you will be taken off this study.

You will have blood drawn (about 1 teaspoon each time) for PD testing. In Cycle 1 before
your daily dose of dasatinib and gemcitabine, PD blood samples will be drawn 1-4 days before
you receive the study drug, on Day 8 (on the day the 1st dose of gemcitabine is given) and
at the end of week 4 before your receive the study drug.

During Week 4 of Cycle 1 and at the end of Cycle 1, you will have a physical exam,
including measurement of your vital signs. You will have blood drawn (about 1 tablespoon)
and urine collected (at the end of Cycle 1 only) for routine tests. You will be asked how
well you are able to perform the normal activities of daily living (a performance status
evaluation) and how you are feeling. You will also be asked about other drugs you may be
taking and if you have had any intolerable side effects from the study drugs.

On Day 1 of all remaining cycles, you will have a physical exam, including measurement of
your vital signs. You will have blood drawn (about 1 teaspoon) for routine tests. You will
have a performance status evaluation and be asked how you are feeling. You will also be
asked about other drugs you may be taking and if you have had any intolerable side effects
from the study drugs.

Once your participation has ended on this study for any reason, you will be asked to have an
end-of-study visit that should occur about 28 days after the last dose of the study drug. At
this visit, you will have a physical exam, including measurement of your vital signs and
weight. You will have a performance status evaluation and be asked how you are feeling.
Blood (about 1 teaspoon) and urine will be collected for routine tests. You will be asked
about other drugs you may be taking, and you will be asked if you have had any intolerable
side effects from the study drugs. Women who are able to have children will again have a
blood (about 1 teaspoon) pregnancy test.

If there are study-related side effects reported at the end-of-study visit, you will
continue to have follow-up visits or telephone calls, (which will last about 5-10 minutes
each time) at least every 4 weeks, to check if you are still experiencing sides effects and
until you no longer experience them.

This is an investigational study. Dasatinib and gemcitabine are both FDA approved and
commercially available. Their use together in this study is experimental and authorized for
use in research only. Up to 63 patients will take part in this study. All will be enrolled
at M. D. Anderson.


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 institutional upper limit upper limit of normal (ULN), b) alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) Exception: patients with primary liver tumors or known liver metastases: times the institutional ULN for total bilirubin, AST and ALT

9. Adequate renal function defined as serum creatinine 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
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.)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated combination doses (MTD)

Outcome Time Frame:

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

Safety Issue:

Yes

Principal Investigator

David S. Hong, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2006-0574

NCT ID:

NCT00429234

Start Date:

January 2007

Completion Date:

February 2013

Related Keywords:

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

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030