Ovarian Cancer MedDRA version: 16.1 Level: LLT Classification code 10033130 Term: Ovarian cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Product Code: GSK2110183
Pharmaceutical Form: Capsule
INN or Proposed INN: GSK2110183
Current Sponsor code: GSK2110183B
Concentration un
Sponsors
Accenture
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase I – Dose Escalation 1. Female at least 18 years of age at the time of signing the informed consent form and capable of giving written informed consent, which includes willingness to comply with the requirements and restrictions listed in the consent form 2. Histologically or cytologically confirmed serous ovarian cancer (including primary peritoneal and Fallopian tube) 3. No more than 2 prior cytotoxic chemotherapeutic regimens 4. Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception, during the study and for 30 days following the last dose of study treatment. 5. Performance Status score of 0-2 according to the Eastern Cooperative Oncology Group (ECOG) scale. 6. Able to swallow and retain oral medication. 7. Subjects diagnosed previously with Type 2 diabetes must have been diagnosed = 6 months prior to enrollment. 8. All 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. The only exception to the Grade 2 rule is peripheral neuropathy. Subjects with peripheral neuropathy = Grade 2 will NOT be eligible. 9. Adequate organ system function Phase II 10. Subjects must have platinum-resistant disease as defined by the following: • Documented response (complete or partial response by RECIST) to at least one prior platinum-based therapy • Progression defined by either (1) RECIST v1.1 criteria or (2) GCIG CA 125 criteria in association with symptoms necessitating treatment -- between 1 and 6 months of prior platinum-based therapy either in the adjuvant or metastatic setting. Subjects will be required to start on treatment for this trial within 8 months after the last platinum-based therapy and may not have had any other anti-cancer therapy in that intervening time. •Subjects are allowed to have a maximum of one non-platinum-based therapy between the onset of platinum resistance as defined above and enrolment. Maintenance therapy defined as extension of at least one component of the treatment regimen will count towards the maximum. For example, if a subject is being treated with cisplatin + pegylated doxorubicin and continues on pegylated doxorubicin for an additional two months after cisplatin is discontinued, the single agent pegylated doxorubicin would be considered the "one non-platinum-based therapy" for the purposes of enrolment. • Subjects must have radiologically measurable disease i.e. presenting with at least one measurable lesion per RECIST 1.1. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. History of another malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. 2. Any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures as determined by the referring physician in collaboration with the medical monitor. 3. Current use of prohibited medication during treatment with study drugs. 4. Chemotherapy, immunotherapy, or other anti-cancer therapy including investigational drugs within 14 days prior to the first dose of any one of the study drugs described in this study. • Radiotherapy prior to initiation of therapy is allowed to a limited area (e.g., palliative treatment for painful bone metastases), if it is not the sole site of disease. Subjects must have completed treatment at least 14 days prior to starting study drugs, and must have recovered from all treatment-related toxicities. 5. Any contraindications (as identified by the investigator) to the doses of carboplatin and/or paclitaxel defined in the protocol 6. Any history of reduction in standard of care paclitaxel dose for peripheral neuropathy. 7. No known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs similar or related to GSK2110183. 8. No known delayed hypersensitivity reaction or idiosyncratic reaction to drugs similar to carboplatin or paclitaxel. Subjects with a history of acute hypersensitivity reactions to carboplatin or paclitaxel are allowed to enroll if their symptoms can be controlled by supportive care interventions or a desensitization protocol per the local medical practice. 9. Prior use of an investigational or licensed drug that targets AKT including perifosine. 10. Presence of active gastrointestinal disease or other condition that could affect gastrointestinal absorption (e.g. malabsorption syndrome) or predispose subject to gastrointestinal ulceration. 11. Evidence of mucosal or internal bleeding. 12. Any major surgery within the last four weeks. 13. Known active infection requiring parenteral or oral anti-infective treatment. 14. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease, unstable hypertension). 15. Subjects with brain metastases and/or leptomeningeal disease are excluded. 16. QTcF interval = 470 msecs. 17. Subjects with bundle branch block or pacemaker or clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block 18. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening. 19. Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. 20. Pregnant or lactating female. 21. Any malignancy related to HIV or solid
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Phase I To determine the safety and tolerability of GSK2110183 administered in combination with carboplatin and paclitaxel in subjects with ovarian cancer--which will be used to identify the dosing regimen to be evaluated in Phase II. Primary Phase II To evaluate the clinical efficacy (as measured by overall response rate) of GSK2110183 administered in combination with carboplatin and paclitaxel in subjects with recurrent platinum-resistant ovarian cancer. To evaluate the clinical efficacy (as measured by overall response rate) of GSK2110183 administered in combination with carboplatin and paclitaxel in subjects with platinum refractory ovarian cancer. ; Secondary Objective: To evaluate the safety and tolerability of the dosing combination of GSK2110183 administered in combination with carboplatin & paclitaxel To evaluate the clinical efficacy (as measured by CA 125 responses and response criteria incorporating both CA 125 &RECIST observations) of GSK2110183 administered in combination with carboplatin & paclitaxel in subjects with recurrent platinum-resistant ovarian cancer. To evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant ovarian cancer treated with GSK2110183 in combination with carboplatin & paclitaxel. To evaluate the clinical efficacy (as measured by CA 125 responses & response criteria incorporating both CA 125 and RECIST observations) of GSK2110183 administered in combination with carboplatin & paclitaxel in subjects with platinum-refractory ovarian cancer. To evaluate the PFS of subjects with platinum-refractory ovarian cancer treated with GSK2110183 in combination with carboplatin & paclitaxel ; Primary end point(s): Phase I Dose Escalation AEs, SAEs, dose reduction or delays, withdrawals due to toxicities | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase II Efficacy AEs, SAEs, dose reduction or delays, withdrawals due to toxicities and changes in laboratory values and vital signs. Response rate (RRCA 125) as defined by GCIG CA 125 criteria. Response rate (RR) as defined by a combination of RECIST 1.1 criteria and CA 125 criteria. PFS is defined as the interval between date of treatment and the earliest date of disease progression by either RECIST 1.1 or CA 125 or death due to any cause. PFSRECIST is defined as the interval between date of treatment and the earliest date of disease progression by RECIST v1.1 or death due to any cause. The median PFSRECIST at 6 months will be evaluated. ;Timepoint(s) of evaluation of this end point: As defined in the protocol | — |
Countries
Australia, Russian Federation, United Kingdom
Contacts
Public ContactStudy Start Up Lead
INC Research
Outcome results
None listed