Clinical trial · Interventional
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
NCT01653912CI-TRIAL-00032321completedPhase 1 / Phase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
* 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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Recurrent Platinum-resistant Ovarian Cancer | Platinum-Resistant Ovarian Carcinoma | CURATED_BROADER | 0.78 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| GSK2110183 in combination with carboplatin and paclitaxel | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- GSK2110183, carboplatin and paclitaxel
- description
- 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.
- interventionNames
- Drug: GSK2110183 in combination with carboplatin and paclitaxel
Primary outcomes (5)
- measure
- Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
- timeFrame
- Up to Week 3
- measure
- Phase 1 Safety: Number of Subjects Reporting Adverse Events
- timeFrame
- Up to Week 3
- description
- 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: * Grade 3 or 4 non-hematologic toxicity as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0, 2009 \[NCI, 2009\] with the exceptions of Grade 3 electrolyte disturbances that respond to correction within 24 hours; or Grade 3 rash, diarrhea, nausea, vomiting and mucositis that responded to standard medical supportive care within 48 hours). * Grade 4 neutropenia lasting ≥5 days * Febrile neutropenia * Grade 3 thrombocytopenia with bleeding * Grade 4 thrombocytopenia * Grade 4 anemia * Treatment delay of \>14 days due to unresolved toxicity * Alanine aminotransferase (ALT) \>3 times upper limit of normal (ULN) with bilirubin \>2 times ULN
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (1)
- DERIVEDBlagden SP, Hamilton AL, Mileshkin L, Wong S, Michael A, Hall M, Goh JC, Lisyanskaya AS, DeSilvio M, Frangou E, Stronach EA, Gopalakrishna P, Meniawy TM, Gabra H. Phase IB Dose Escalation and Expansion Study of AKT Inhibitor Afuresertib with Carboplatin and Paclitaxel in Recurrent Platinum-resistant Ovarian Cancer. Clin Cancer Res. 2019 Mar 1;25(5):1472-1478. doi: 10.1158/1078-0432.CCR-18-2277. Epub 2018 Dec 18. PMID 30563934