Dose-finding Study in Platinum-Resistant Ovarian Cancer

• Status: Completed
• Trial end date: 2015-11-01
• Target enrollment: 0
• Participant gender: Female

Summary

• 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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Accenture
• Treatments: Albumin-Bound Paclitaxel; Carboplatin; Paclitaxel

Criteria

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