Dose-finding Study in Platinum-Resistant Ovarian Cancer

NCT ID: NCT01653912

Last Updated: 2018-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2015-11-30

Brief 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.

Detailed 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.

Conditions

Recurrent Platinum-resistant Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GSK2110183 in combination with carboplatin and paclitaxel

Intervention Type: DRUG

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.

Interventions

GSK2110183 in combination with carboplatin and paclitaxel

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.

Intervention Type: DRUG

Other Intervention Names

Taxol (paclitaxel); Paraplatin (carboplatin); AKT Inhibitor

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Accenture

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard A Brigandi, MD, PhD, FAAP

Role: STUDY_DIRECTOR

GlaxoSmithKline

Anne L Hamilton

Role: PRINCIPAL_INVESTIGATOR

Royal Women's Hospital

Sarah P Blagden

Role: PRINCIPAL_INVESTIGATOR

Imperial College Healthcare NHS Trust

Linda Mileshkin

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

Shirley S Wong

Role: PRINCIPAL_INVESTIGATOR

Western Hospital

Andrew Dean

Role: PRINCIPAL_INVESTIGATOR

Sir Charles Gairdner Hospital

Marcia Hall

Role: PRINCIPAL_INVESTIGATOR

Mount Vernon Cancer Center

Bhawana Awasthy, MD

Role: STUDY_DIRECTOR

Syneos Health

Locations

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Western Hospital

Footscray, Victoria, Australia

Royal Women's Hospital

Parkville, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Medical Radiology Scientific Center of Ministry of Healthcare and Social Development of RF

Omskaya, , Russia

City Clinical Oncology Dispensary

Saint Petersburg, , Russia

Mount Vernon Cancer Center

Northwood, Middlesex, London, United Kingdom

Royal Surrey County Hospital NHS Foundation Trust

Guildford, Surry, United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

Australia; Russia; United Kingdom

References

Blagden 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.

Reference Type: DERIVED

PMID: 30563934 (View on PubMed)

Other Identifiers

2012-002483-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PKB116611

Identifier Type: -

Identifier Source: org_study_id