MDACC Study Summary 2006-0574

Study Summary
No. 2006-0574:.......Advanced Cancers; Solid Tumors......David S. Hong......Investigational Cancer Therapeutics

Study Summary Title



Study Summary Number:	2006-0574

Study Title:	Phase I Open-labeled Trial of Gemcitabine and Dasatinib in Advanced Solid Tumors

Physician

New Patient Referral



Name:	David S. Hong	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Investigational Cancer Therapeutics	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-563-0181 Contact us about clinical trials

General Information



Disease Group:	Advanced Cancers Solid Tumors	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	Once weekly for Gemcitabine infusion.

Treatment Agents:	Dasatinib Gemcitabine	Home Care:	They patient will take oral tablets of dasatinib at home once daily.

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	N/A

Description/
Intervention:

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.

Study Objectives / Outcomes

Primary Objectives
1) To determine the maximum tolerated combination doses (MTD), dose-limiting toxicity (DLT), and recommended Phase II combination doses of gemcitabine with dasatinib in patients with advanced solid tumors.

Secondary Objectives
1) To determine response signals based on modified RECIST criteria

Study Status Information



Study Activation / Registration Date:	01/26/2007

IRB Review and Approval Date:	09/06/2006

Study Type:	Phase I

Recruitment Status:	Closed

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Signed written informed consent

2) Available for protocol-required follow-up

3) 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 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 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 FNA biopsable 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 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 P.I.

Links

Registration Number: NCT00429234
Study Information on Clinical Trials Registry (clinicaltrials.gov)