Phase I Study to Assess the Safety, Pharmacokinetics, & Pharmacodynamics of GSK923295 in Subjects w/ Refractory Cancer

Completed · Phase 1

Conditions studied: Cancer

In brief

This is a Phase I, open-label, first time in human study of GSK923295, in adult subjects with cancers that do not respond to standard therapy. This study will be conducted in two stages; a dose-escalation stage (Stage 1) and an expansion cohort stage (Stage 2).

Key facts

Study ID

NCT00504790

Run by

GlaxoSmithKline

People needed

39

Starts

2007-06-25

Expected to finish

2012-05-08

Last updated by the study team

2018-07-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed, written informed consent provided.
• a) Stage 1 Subjects: Histologically or cytologically confirmed diagnosis of solid tumor malignancy that is not responsive to accepted standard therapies, or for which there is no standard therapy.
• b) Stage 2 Subjects: Histologically or cytologically confirmed diagnosis of solid tumor malignancy, non-Hodgkin's lymphoma, or chronic lymphocytic leukemia that is not responsive to accepted standard therapies, or for which there is no standard therapy.
• Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
• 18 years old or older.
• Male or female
• A female is eligible to enroll in the study if she is of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who:
• Has had a hysterectomy, or
• Has had a bilateral oophorectomy (ovariectomy), or
• Has had a bilateral tubal ligation, or
• Is post-menopausal (demonstrate total cessation of menses for greater than or equal to one year).
• Childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following from at least two weeks prior to study enrolment until completion of the Post Study procedures:
• An intrauterine device (IUD) with a documented failure rate of less than 1% per year.
• Vasectomized partner who is sterile and is the sole sexual partner for that woman.
• Complete abstinence from sexual intercourse.
• Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm.
• A male is eligible to enter and participate in the study if he either agrees to abstain from sexual intercourse or use a condom and occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository from the first dose administered until completion of the Post-Treatment procedures; or is surgically sterile.
• Adequate organ systems function as defined in the protocol.
• Subjects may have measurable lesions according to RECIST criteria in Stage 1. It is required in Stage 2 that subjects with solid tumors have measurable lesions according to RECIST criteria.
• Paraffin-embedded archival tumor tissue available for testing.
• At least one target tumor accessible to serial core needle biopsies at study entry (screening) and one additional time point post-dose Cycle 1. Note: optional for Stage 1 (Dose Escalation); it is mandatory for Stage 2 (Expansion Cohort)

You may not qualify if…

• A subject will not be eligible for inclusion in this study if any of the following criteria apply:
• Any major surgery OR prior anti-cancer therapy including but not limited to chemotherapy, radiotherapy, immunotherapy, biological therapy, or investigational therapy within the past 28 days (42 days for prior nitrosureas or mitomycin C).
• Prior allogeneic or autologous bone marrow transplant.
• Greater than 30% bone marrow irradiated.
• Unresolved toxicity ≥ Grade 2 from previous anti-cancer therapy (except alopecia).
• History of hemolytic anemia (either congenital or acquired) OR current laboratory evidence of hemolysis (Grade 1CTCAE or greater) that includes at least one of the following:
• Decrease in serum haptoglobin (outside normal institutional laboratory values)
• Increase in indirect bilirubin (outside normal institutional laboratory values)
• Peripheral blood smear consistent with hemolysis (presence of schistocytes)
• Pre-existing peripheral neuropathy or other neurological toxicity ≥ Grade 2.
• Female subjects who are pregnant or lactating.
• Any serious or unstable pre-existing medical, psychiatric, active infection or other condition (including lab abnormalities) that could interfere with subject safety or obtaining informed consent.
• Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
• QTc prolongation defined as a QTc interval greater than or equal to 450 msecs.
• Other significant ECG abnormalities including 2nd or 3rd degree AV block or bradycardia (ventricular rate less than 50 beats/min).
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within the past 6 months.
• For subjects with a history of myocardial infarction, congestive heart failure, abnormal left ventricular ejection fraction (LVEF), or prior anthracycline exposure, LVEF must be assessed within 28 days of the first dose of study drug by one of the following methods: MUGA or ECHO. An LVEF measurement of < 50% will exclude the subject from participation in the study.
• Class III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Current use of warfarin ≥ 4 mg per day. NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted. PT/PTT must meet the inclusion criteria.
• Current use of prohibited medications in accordance with the guidelines detailed in the protocol in the "Prohibited Medications" section.
• Current use of drugs with risk of torsade de pointes as described in the protocol.
• Evidence of symptomatic or untreated central nervous system involvement (i.e., brain metastases, leptomeningeal disease, cord compression).

Where it is running

• GSK Investigational Site — Duarte, California, United States
• GSK Investigational Site — Detroit, Michigan, United States
• GSK Investigational Site — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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