Dose-finding Study in Platinum-Resistant Ovarian Cancer

Accenture

Status and phase: Completed; Phase 2; Phase 1

Conditions: Recurrent Platinum-resistant Ovarian Cancer

Treatments: Drug: GSK2110183 in combination with carboplatin and paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01653912

2012-002483-27 (EudraCT Number)

PKB116611

Details and patient eligibility

About

• 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.

Full description

PKB116611 is an open-label Phase I/II study of the investigational drug GSK2110183 given in combination with carboplatin and paclitaxel to subjects with recurrent ovarian cancer. Phase I is a dose escalation evaluation of daily oral doses of GSK2110183 administered in combination with every 3 week carboplatin and paclitaxel to any subject with recurrent ovarian cancer. Phase II is a single arm evaluation of the clinical efficacy of the combination identified in Phase I to subjects with platinum-resistant ovarian cancer.

Enrollment: 59 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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59 participants in 1 patient group

GSK2110183, carboplatin and paclitaxel

Experimental group

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.

Treatment:

Drug: GSK2110183 in combination with carboplatin and paclitaxel