MDACC Study Summary 2008-0061 (Archived)

Study Summary
No. 2008-0061:.......Advanced Cancers; Lymphoma......Razelle Kurzrock......Investigational Cancer Therapeutics

Study Summary Title



Study Summary Number:	2008-0061

Study Title:	A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK1059615 in Patients with Solid Tumors or Lymphoma

Physician

New Patient Referral



Name:	Razelle Kurzrock	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:	713-563-1930 Contact us about clinical trials

General Information



Disease Group:	Advanced Cancers Lymphoma	Supported By:	GlaxoSmithKline

Phase of Study:	Phase I/Phase II	Return Visit:	Patients will be in clinic on Day 1, sometime between Days 3-5, Day 8, Day 15 and Day 22 of the first cycle; weekly during cycle 2; every 4 weeks for all subsequent cycles; and at end of study (21 days after last dose of treatment drug.)

Treatment Agents:	GSK1059615	Home Care:	Patients will take the study drug twice daily at home on days they are not in the clinic.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

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 GSK1059615 that can be given to patients with advanced cancer. The safety of this drug will also be studied.

Study Objectives / Outcomes

Primary Objective:

To determine the safety, tolerability, and the recomended Phase II dose of GSK1059615 given orally for 21 days on and 7 days off per cycle.

Secondary Objective:

To characterize the pharmacokinetics of GSK1059615 after single- and repeat-dose administration
To identify a range of biologically active doses
To evaluate clinical efficacy after treatment with GSK1059615
To explore relationships between GSK1059615 PK (pharmacokinetic), PD (pharmacodynamic), and clinical endpoints

Translational Objective:

To explore the association of biologic/clinical endpoints with DNA/protein profiles from tumor and/or blood

Study Status Information



Study Activation / Registration Date:	07/14/2008

IRB Review and Approval Date:	06/18/2008

Study Type:	Phase I

Recruitment Status:	Terminated

Projected Accrual:	70

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) 18 years old or older

2) Histologically- or cytologically- confirmed diagnosis of solid tumor malignancy or lymphoma that is not responsive to accepted standard therapies or for which there is no standard or curative therapy.

3) Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.

4) Able to swallow and retain oral medication.

5) A male is eligible to enter and participate in the study if he either agrees to abstain from sexual intercourse from the first dose of study drug and until 21 days after the last dose of study medication; or agrees to use a condom and occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository from the first dose of study drug and until 21 days after the last dose of study medication; or is surgically sterile.

6) A female is eligible to enroll in the study if she is of non-child-bearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who is characterized by at least one of the following: 1) has had a hysterectomy, 2) has had a bilateral oophorectomy (ovariectomy), 3) has had a bilateral tubal ligation, or 4) is post-menopausal (total cessation of menses for >/= 1 year).

7) Women of childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following from >/= 2 weeks prior to the first dose of study drug and until 21 days after the last dose of study medicaton: 1) use an intrauterine device (IUD) with a documented failure rate of < 1% per year; 2) have intercourse only with a vasectomized partner who is sterile and is the sole sexual partner for that woman; 3) complete abstinence from sexual intercourse;

8) 8 continued: or 4) use double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm.

9) Adequate organ system function as defined:1) Hematologic: Absolute neutrophil count >/= 1.5 x 10^9/L, Hemoglobin >/= 9 g/dL, Platelets >/= 75 x 10^9/L, PT/INR and PTT </= 1.3 x ULN; 2) Hepatic: Total bilirubin </= 1.5 x ULN, AST AND ALT </= 2.5 x ULN (can be higher in presence of liver metastases); 3) Renal: Creatinine </= ULN, or calculated creatinine clearance or 24 hour urine creatinine clearance >/= 60mL/min; urine microalbumin:creatinine < 300 mg/g; and 4) Cardiac: ejection fraction >/= LLN by ECHO, Troponin </= ULN

Exclusion Criteria:

1) Use of an investigational anti-cancer drug within 28 days or 5 half-lives preceding the first dose of GSK1059615.

2) Chemotherapy within the last 3 weeks (6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity are permitted with approval of the GSK medical monitor if administered at least 2 weeks prior to the first dose of study drug.

3) Trastuzumab within the last 4 weeks.

4) Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks.

5) Prior use of any PI3K inhibitor.

6) Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug. (To date there are no known FDA-approved drugs chemically related to GSK1059615).

7) Current use of a prohibited medication or requires any of these medications during treatment with GSK1059615.

8) Current use of warfarin for therapeutic anticoagulation.

9) Presence of an active gastrointestinal disease or other condition known to interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.

10) Unresolved toxicity greater than Grade 1 from previous anti-cancer therapy except alopecia. Patients with stable Grade 2 neuropathy can be enrolled with approval by the GSK Medical Monitor.

11) QTc interval >/= 450 msecs for men and QTc interval >/= 470 msecs for women.

12) History of acute coronary syndromes (including unstable angina and myocardial infarction), atrial fibrillation, coronary angioplasty, or stenting within the past 24 weeks.

13) Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.

14) Symptomatic or untreated leptomeningeal or brain metastases. Patients previously treated for these conditions who are asymptomatic and off of corticosteroid and P450-inducing anti-epileptic medication for at least 2 months are permitted.

15) Primary malignancy of the central nervous system.

16) Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

17) Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.

18) Nursing female.

Links

Registration Number: NCT00695448
Study Information on Clinical Trials Registry (clinicaltrials.gov)