- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01653912
Dose-finding Study in Platinum-Resistant Ovarian Cancer
An Open-Label Phase I/II Study of GSK2110183 in Combination With Carboplatin and Paclitaxel in Subjects With Platinum-Resistant Ovarian Cancer
- Dose-finding study of GSK2110183 administered in combination with carboplatin and paclitaxel to any subject with recurrent ovarian cancer.
- Safety and efficacy study of GSK2110183 administered in combination with carboplatin and paclitaxel to subjects with platinum-resistant ovarian cancer.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Queensland
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Herston, Queensland, Australia, 4029
- Royal Brisbane and Women's Hospital
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Victoria
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East Melbourne, Victoria, Australia, 8006
- Peter MacCallum Cancer Centre
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Footscray, Victoria, Australia, 3011
- Western Hospital
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Parkville, Victoria, Australia, 3052
- Royal Women's Hospital
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Sir Charles Gairdner Hospital
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Omskaya, Russian Federation, 249036
- Medical Radiology Scientific Center of Ministry of Healthcare and Social Development of RF
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Saint-Petersburg, Russian Federation, 198255
- City Clinical Oncology Dispensary
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London, United Kingdom, W 12 0HS
- Imperial College Healthcare NHS Trust
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London
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Northwood, Middlesex, London, United Kingdom, HA6 2RN
- Mount Vernon Cancer Center
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Surry
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Guildford, Surry, United Kingdom, GU2 7XP
- Royal Surrey County Hospital NHS Foundation Trust
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Phase I Inclusion Criteria:
- Female, 18 years of age as of signing the informed consent form, capable of giving/complying with written informed consent
- Histologically or cytologically confirmed serous ovarian cancer (includes primary peritoneal and Fallopian tube)
- Negative serum pregnancy test in women of childbearing potential within 14 days of first dose of treatment, agree to use effective contraception during/after (6 months post dose of paclitaxel or 30 days post dose GSK2110183 whichever is longer)
- Performance Status score of 0-2 according to the ECOG scale.
- Able to swallow and retain oral medication
- Subjects diagnosed previously with Type 2 diabetes must have been diagnosed ≥ 6 months prior to enrollment
- Prior treatment-related toxicities (except for alopecia) must be ≤ Grade 1 according to NCI-CTCAE (Version 4.0 [NCI, 2009]) at the time of treatment allocation OR ≤ Grade 2 and stable for 4 weeks or longer at the time of screening evaluation. Exception: Subjects with peripheral neuropathy >/= Grade 2 will NOT be eligible
- Adequate organ system function
Phase II Inclusion Criteria:
Cohort A
- Phase I criteria
- Documented complete or partial response by RECIST to at least 1 prior platinum-based therapy
- Progression defined by either (1) RECIST v1.1 criteria or (2) GCIG CA 125 criteria associated with symptoms necessitating treatment between 1 and 6 months of prior platinum-based therapy either in adjuvant or metastatic setting
- Subjects allowed to have a maximum of one non-platinum-based therapy between the onset of platinum resistance
- Must have radiologically measurable disease i.e. presenting with at least one measurable lesion per RECIST 1.1
Cohort B
- Phase I criteria
- Documented complete or partial response by RECIST to at least 1 prior platinum-based therapy
- Progression defined by either (1) RECIST v1.1 criteria or (2) GCIG CA 125 criteria associated with symptoms necessitating treatment while being treated with a regimen containing carboplatin and paclitaxel (or within 4 weeks of completing treatment)
- Subjects will be required to start on treatment within 8 weeks after the last infusion of chemotherapy and may not have had any other anti-cancer therapy in the intervening time
- Must have radiologically measurable disease i.e. presenting with at least one measurable lesion per RECIST 1.1
- Additional restrictions on number of prior therapies may be added to eligibility criteria based on emerging data
Exclusion Criteria:
- History of another malignancy (some exceptions may apply)
- Serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
- Current use of prohibited medication during treatment.
- Chemotherapy, immunotherapy, or other anti-cancer therapy within 14 days prior to the first dose study drug
- Radiotherapy prior to initiation of therapy (some exceptions may apply)
- Contraindications (identified by the investigator) to the doses of carboplatin and/or paclitaxel
- History of reduction in standard of care paclitaxel dose for peripheral neuropathy
- No known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs similar or related to GSK2110183
- No known delayed hypersensitivity reaction or idiosyncratic reaction to drugs similar to carboplatin or paclitaxel (some exceptions may apply)
- Prior use of a drug that targets AKT including perifosine
- History of Type 1 diabetes
- Gastrointestinal disease or other condition that could affect absorption or predispose subject to gastrointestinal ulceration
- Mucosal or internal bleeding
- Major surgery within the last four weeks
- Infection requiring parenteral or oral anti-infective treatment
- Severe or uncontrolled systemic diseases
- Brain metastases and/or leptomeningeal disease
- QTcF interval ≥ 470 msecs
- Bundle branch block, pacemaker or clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block
- History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty,stenting or bypass grafting within six months of Screening
- Class II, III or IV heart failure as defined by the NYHA functional classification system
- Pregnant or lactating female
- Malignancies related to HIV or solid organ transplant; history of known HIV, history of know HBV surface antigen positivity (subjects with documented laboratory evidence of HBV clearance may be enrolled) or positive HCV antibody
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: GSK2110183, carboplatin and paclitaxel
Subjects will be treated with a maximum of six doses of carboplatin + paclitaxel in combination with continuous daily GSK2110183 followed by single agent GSK2110183 at the single-agent MTD of 125 mg or above oral daily.
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Phase I is a dose escalation evaluation of increasing doses of GSK2110183 administered on a continuous daily schedule in combination with carboplatin AUC 5 and paclitaxel 175mg/m2 given every three weeks for a maximum 6 cycles.
The dosing regimen identified in Phase I will then be evaluated in Phase II, a single arm study focused on clinical efficacy.
Treatment with the three drug regimen will continue for a maximum of 6 x 21 day cycles followed by continuous GSK2110183 at the single agent MTD.
Subjects may continue on study drug until progression, death or unacceptable toxicity.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
Time Frame: Up to Week 3
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Up to Week 3
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Phase 1 Safety: Number of Subjects Reporting Adverse Events
Time Frame: Up to Week 3
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Study Treatment refers to GSK2110183 with or without Carboplatin and/or Paclitaxel. Dose limiting toxicity (DLT): An event is considered a DLT if it had a reasonable causal relationship to study drug & occurs within first 3 weeks of therapy & met at least one of the following criteria:
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Up to Week 3
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Phase 1: Maximum Tolerated Dose (MTD) of GSK2110183
Time Frame: Up to Week 3
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MTD is defined as the highest dose at which 1 or fewer of up to 6 subjects experience a dose limiting toxicity (DLT) during the first 3 weeks of combination therapy.
MTD was considered exceeded if 2 or more subjects in a cohort of up to 6 subjects experienced a DLT.
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Up to Week 3
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Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)
Time Frame: Every 3 weeks up to 6 months
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Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is Disappearance of all target lesions and Partial Response (PR) is greater than or equal to (≥) 30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR. |
Every 3 weeks up to 6 months
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ORR in Phase 2 Subjects With Recurrent Platinum-refractory Ovarian Cancer (Cohort B)
Time Frame: Every 3 weeks up to 6 months
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Per RECIST version 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is Disappearance of all target lesions and Partial Response (PR) is ≥30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR. |
Every 3 weeks up to 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer
Time Frame: Up to Week 3
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Per RECIST version 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is disappearance of all target lesions and Partial Response (PR) is ≥30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR. |
Up to Week 3
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Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
Time Frame: Up to Day 21 (Phase 2)
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Up to Day 21 (Phase 2)
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Phase 2 Safety: Number of Subjects Reporting Adverse Events
Time Frame: Up to Day 51
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Dose limiting toxicity (DLT): An event is considered a DLT if it had a reasonable causal relationship to study drug & occurs within first 3 weeks of therapy & met at least one of the following criteria:
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Up to Day 51
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Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125
Time Frame: From Month 1 to 6
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RR is defined by the percentage of subjects with investigator-assessed Partial Cancer Antigen (CA) 125 Response (PR) or Complete CA 125 Response (CR) at any time during the study by GCIG CA 125.
PR is greater than (>) 50% decrease in CA-125 values from baseline and no clinical or radiological evidence of new lesions.
CR is decrease in the CA-125 to within the normal limits and less than (<) 40 IU/mL and no clinical or radiological evidence of disease.
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From Month 1 to 6
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Progression Free Survival (PFS) by RECIST or Clinical Symptomatic Progression of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A)
Time Frame: From first dose until disease progression or death (approximately 36 months)
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PFS was defined as the number of months between date of first GSK2110183 treatment and the earliest date of disease progression by RECIST or clinical symptomatic progression or death due to any cause whichever is earlier.
Progression is defined using RECIST version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesion in reference to the smallest sum of the longest diameter recorded since the treatment started.
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From first dose until disease progression or death (approximately 36 months)
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PFS by RECIST of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A)
Time Frame: From first dose until disease progression or death (approximately 36 months)
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PFS was defined as the number of months between date of first GSK2110183 treatment and the earliest date of disease progression by RECIST or death due to any cause whichever is earlier.
Progression is defined using RECIST version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesion in reference to the smallest sum of the longest diameter recorded since the treatment started.
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From first dose until disease progression or death (approximately 36 months)
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Richard A Brigandi, MD, PhD, FAAP, GlaxoSmithKline
- Principal Investigator: Anne L Hamilton, Royal Women's Hospital
- Principal Investigator: Sarah P Blagden, Imperial College Healthcare NHS Trust
- Principal Investigator: Linda Mileshkin, Peter MacCallum Cancer Centre, Australia
- Principal Investigator: Shirley S Wong, Western Hospital
- Principal Investigator: Andrew Dean, Sir Charles Gairdner Hospital
- Principal Investigator: Marcia Hall, Mount Vernon Cancer Center
- Study Director: Bhawana Awasthy, MD, Syneos Health
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Carboplatin
- Paclitaxel
- Albumin-Bound Paclitaxel
Other Study ID Numbers
- PKB116611
- 2012-002483-27 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Platinum-resistant Ovarian Cancer
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M.D. Anderson Cancer CenterActive, not recruitingRecurrent Platinum-Resistant Ovarian Carcinoma | Recurrent Fallopian Tube Clear Cell Adenocarcinoma | Recurrent Ovarian Clear Cell Adenocarcinoma | Recurrent Platinum-Resistant Fallopian Tube Carcinoma | Recurrent Platinum-Resistant Primary Peritoneal Carcinoma | Recurrent Primary Peritoneal...United States
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Aduro Biotech, Inc.Incyte CorporationTerminatedPlatinum-resistant Ovarian Cancer | Platinum-resistant Fallopian Cancer | Platinum-resistant Peritoneal CancerUnited States, Canada
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Roswell Park Cancer InstituteActive, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Platinum-Sensitive Ovarian Carcinoma | Refractory Ovarian... and other conditionsUnited States
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National Cancer Institute (NCI)NRG OncologyWithdrawnRecurrent Ovarian High Grade Serous Adenocarcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Recurrent Fallopian Tube Endometrioid Adenocarcinoma | Recurrent Ovarian Endometrioid Adenocarcinoma | Recurrent Platinum-Resistant Fallopian Tube Carcinoma | Recurrent Platinum-Resistant Primary... and other conditionsUnited States
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Northwestern UniversityNational Cancer Institute (NCI); Ipsen BiopharmaceuticalsCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Refractory Ovarian Carcinoma | Refractory Fallopian Tube... and other conditionsUnited States
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Seoul National University HospitalPharos iBio Co., Ltd.RecruitingPlatinum-resistant Ovarian Cancer | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-refractory Ovarian CarcinomaKorea, Republic of
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National Cancer Institute (NCI)Active, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian CarcinomaUnited States
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City of Hope Medical CenterNational Cancer Institute (NCI)Not yet recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian CarcinomaUnited States
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City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Platinum-Resistant Ovarian Carcinoma | Recurrent Platinum-Resistant Fallopian Tube Carcinoma | Recurrent Platinum-Resistant Primary Peritoneal CarcinomaUnited States
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