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Dose-finding Study in Platinum-Resistant Ovarian Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Accenture
ClinicalTrials.gov Identifier:
NCT01653912
First received: July 27, 2012
Last updated: December 18, 2014
Last verified: December 2014
  Purpose
  • 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.

Condition Intervention Phase
Recurrent Platinum-resistant Ovarian Cancer
Drug: GSK2110183 in combination with carboplatin and paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Phase I/II Study of GSK2110183 in Combination With Carboplatin and Paclitaxel in Subjects With Platinum-Resistant Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Accenture:

Primary Outcome Measures:
  • Phase I - Dose Escalation [ Time Frame: Every 3 weeks ] [ Designated as safety issue: Yes ]

    Determine the safety and tolerability of GSK2110183 administered in combination with carboplatin and paclitaxel in subjects with recurrent ovarian cancer which will be used to identify the dosing regimen to be evaluated in Phase II.

    Endpoints:

    AEs, SAEs, dose reduction or delays, withdrawals due to toxicities and changes in laboratory values and vital signs.


  • Phase II - Efficacy [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]

    Evaluate the clinical efficacy (measured by overall response rate) of GSK2110183 administered in combination with carboplatin and paclitaxel in subjects with recurrent platinum-resistant ovarian cancer.

    Endpoint:

    Overall response rate defined as the percentage of subjects with confirmed complete response or partial response using RECIST v1.1.



Secondary Outcome Measures:
  • Phase II - Efficacy [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]

    Evaluate the efficacy (measured by CA 125 responses and response criteria incorporating both CA125 and RECIST observations) of GSK2110183 administered in combination with carboplatin and paclitaxel in subjects with recurrent platinum-resistant ovarian cancer. Evaluate the (6 month) progression free survival of subjects with recurrent platinum-resistant ovarian cancer treated with GSK2110183 in combination with carboplatin and paclitaxel.

    Endpoints:

    Response rate as defined by GCIG CA 125 criteria and combination of RECIST 1.1 criteria and CA 125 criteria.


  • Phase II - Safety [ Time Frame: Every 3 weeks ] [ Designated as safety issue: Yes ]

    To evaluate the safety and tolerability of the dosing combination of GSK2110183 administered in combination with carboplatin and paclitaxel identified in Phase I.

    Endpoints:

    AEs, SAEs, dose reduction or delays, withdrawals due to toxicities and changes in laboratory values and vital signs



Estimated Enrollment: 60
Study Start Date: December 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other Names:
  • Taxol (paclitaxel)
  • Paraplatin (carboplatin)
  • AKT Inhibitor

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01653912

Locations
Australia, Queensland
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia, 4029
Australia, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 8006
Western Hospital
Footscray, Victoria, Australia, 3011
Royal Women's Hospital
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Russian Federation
Medical Radiology Scientific Center of Ministry of Healthcare and Social Development of RF
Omskaya, Russian Federation, 249036
City Clinical Oncology Dispensary
Saint-Petersburg, Russian Federation, 198255
United Kingdom
Mount Vernon Cancer Center
Northwood, Middlesex, London, United Kingdom, HA6 2RN
Royal Surrey County Hospital NHS Foundation Trust
Guildford, Surry, United Kingdom, GU2 7XP
Imperial College Healthcare NHS Trust
London, United Kingdom, W 12 0HS
Sponsors and Collaborators
Accenture
Investigators
Study Director: Richard A Brigandi, MD, PhD, FAAP GlaxoSmithKline
Principal Investigator: Anne L Hamilton Royal Women's Hospital
Principal Investigator: Sarah P Blagden Imperial College Healthcare NHS Trust
Principal Investigator: Linda Mileshkin Peter MacCallum Cancer Centre, Australia
Principal Investigator: Shirley S Wong Western Hospital
Principal Investigator: Andrew Dean Sir Charles Gairdner Hospital
Principal Investigator: Marcia Hall Mount Vernon Cancer Center
Study Director: Bhawana Awasthy, MD INC Research
  More Information

No publications provided

Responsible Party: Accenture
ClinicalTrials.gov Identifier: NCT01653912     History of Changes
Other Study ID Numbers: PKB116611, 2012-002483-27
Study First Received: July 27, 2012
Last Updated: December 18, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Russia: Ministry of Health of the Russian Federation

Keywords provided by Accenture:
cancer
ovarian
platinum-resistant

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on March 01, 2015