Last updated: 11/04/2018 05:59:44
Phase I Study to Assess the Safety, Pharmacokinetics, & Pharmacodynamics of GSK923295 in Subjects w/ Refractory Cancer
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase I, Open-Label, Dose-Escalation, First Time in Human Study to Evaluate the Safety Profile, Pharmacokinetics, and Pharmacodynamics of GSK923295 in Subjects with Refractory Cancers
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Safety: - physical exam
Timeframe: at screen & Day(D) 1 of each cycle and follow-up(F/U)
- vital signs and lab tests
Timeframe: at screen & D1, 8, 15, & 22 for each cycle & F/U
- ECGs
Timeframe: at screen and D1, 8 & 15 for each cycle & F/U
continuous monitoring of adverse events
Timeframe: each visit
Secondary outcomes:
Plasma samples of GSK923295 taken at:
Timeframe: - Day 1 & 15 (Cycle 1) for Stage 1
Plasma samples of GSK923295 taken at:
Timeframe: - Day 1 of each cycle for Stage 2
Interventions:
Enrollment:
39
Primary completion date:
2012-08-05
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Chung V, Fleming RA, Johnson BM, Gauvin J, Cyr TL, Lager JJ, Lu E, Alberti DB, Williams B, Weber BL, Synold T, Holen KD. A phase 1 and first time in human study of the centromere associated protein E (CENP-E) inhibitor GSK923295A in patients with advanced solid rumors. American Association of Clinical Research Annual Meeting 2008, Oral Presentation, Abstract LB 246
Fleming RA, Holen KD, Cyr TL, Johnson BM, Gauvin JL, Lager JJ, Williams B, Alberti DB, Weber BL, Grilley-Olson JE, Chung V. A phase I dose escalation and pharmacokinetic study of the novel mitotic checkpoint inhibitor GSK923295A in patients with solid tumors. (Poster). EORTC/NCI/AACR Molecular Targets and Cancer Therapeutics Meeting, Geneva, Switzerland, 2008
Holen KD, Heath E, Shelman WS, Kirby LC, Johnson BM, Botbyl JD, Grilley-Olson JE, Lampkin TA, Chung V. Phase I, first-in-human study of the centromere-associated protein e (CENP-E) inhibitor GSK923295 in patients with advanced solid tumors (Study CPE107602). American Society of Clinical Oncology 2010, Oral Presentation, Abstract 3012
Vincent Chung, Elisabeth Heath, William Schelman, Brendan Johnson, Lyndon Kirby, Kerlin Lynch, Jeffrey Botbyl, Thomas Lampkin, Kyle Holen.First-Time-In-Human Study of GSK923295, a Novel Anti-Mitotic Inhibitor of Centromere-Associated Protein E (CENP-E), in Patients with Refractory Cancer.Cancer Chemotherapy and Pharmacology.2012;69(3):733-741.
Medical condition
Cancer
Product
GSK923295
Collaborators
Not applicable
Study date(s)
June 2007 to May 2012
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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).
Inclusion and exclusion criteria
Inclusion criteria:
- 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
- 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)
A female is eligible to enroll in the study if she is of:
Exclusion criteria:
- 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).
- 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).
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:
Trial location(s)
Location
GSK Investigational Site
Detroit, Michigan, United States, 48201
Status
Study Complete
Location
GSK Investigational Site
Duarte, California, United States, 91010
Status
Study Complete
Location
GSK Investigational Site
Madison, Wisconsin, United States, 53792-5666
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
2012-08-05
Actual study completion date
2012-08-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Results for study CPE107602 can be found on the GSK Clinical Study Register.
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