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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01653912




Registration number
NCT01653912
Ethics application status
Date submitted
27/07/2012
Date registered
31/07/2012
Date last updated
2/04/2018

Titles & IDs
Public title
Dose-finding Study in Platinum-Resistant Ovarian Cancer
Scientific title
An Open-Label Phase I/II Study of GSK2110183 in Combination With Carboplatin and Paclitaxel in Subjects With Platinum-Resistant Ovarian Cancer
Secondary ID [1] 0 0
2012-002483-27
Secondary ID [2] 0 0
PKB116611
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Platinum-resistant Ovarian Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2110183 in combination with carboplatin and paclitaxel

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.


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (=) 3 in Severity
Timepoint [1] 0 0
Up to Week 3
Primary outcome [2] 0 0
Phase 1 Safety: Number of Subjects Reporting Adverse Events - Study Treatment refers to GSK2110183 with or without Carboplatin and/or Paclitaxel.
Dose limiting toxicity (DLT): An event is considered a DLT if it had a reasonable causal relationship to study drug & occurs within first 3 weeks of therapy & met at least one of the following criteria:
Grade 3 or 4 non-hematologic toxicity as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0, 2009 [NCI, 2009] with the exceptions of Grade 3 electrolyte disturbances that respond to correction within 24 hours; or Grade 3 rash, diarrhea, nausea, vomiting and mucositis that responded to standard medical supportive care within 48 hours).
Grade 4 neutropenia lasting =5 days
Febrile neutropenia
Grade 3 thrombocytopenia with bleeding
Grade 4 thrombocytopenia
Grade 4 anemia
Treatment delay of >14 days due to unresolved toxicity
Alanine aminotransferase (ALT) >3 times upper limit of normal (ULN) with bilirubin >2 times ULN
Timepoint [2] 0 0
Up to Week 3
Primary outcome [3] 0 0
Phase 1: Maximum Tolerated Dose (MTD) of GSK2110183 - MTD is defined as the highest dose at which 1 or fewer of up to 6 subjects experience a dose limiting toxicity (DLT) during the first 3 weeks of combination therapy. MTD was considered exceeded if 2 or more subjects in a cohort of up to 6 subjects experienced a DLT.
Timepoint [3] 0 0
Up to Week 3
Primary outcome [4] 0 0
Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A) - Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is Disappearance of all target lesions and Partial Response (PR) is greater than or equal to (=) 30% decrease in the sum of the longest diameter of target lesions.
Overall Response (OR) = CR + PR.
Timepoint [4] 0 0
Every 3 weeks up to 6 months
Primary outcome [5] 0 0
ORR in Phase 2 Subjects With Recurrent Platinum-refractory Ovarian Cancer (Cohort B) - Per RECIST version 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is Disappearance of all target lesions and Partial Response (PR) is =30% decrease in the sum of the longest diameter of target lesions.
Overall Response (OR) = CR + PR.
Timepoint [5] 0 0
Every 3 weeks up to 6 months
Secondary outcome [1] 0 0
ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer - Per RECIST version 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is disappearance of all target lesions and Partial Response (PR) is =30% decrease in the sum of the longest diameter of target lesions.
Overall Response (OR) = CR + PR.
Timepoint [1] 0 0
Up to Week 3
Secondary outcome [2] 0 0
Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade =3 in Severity
Timepoint [2] 0 0
Up to Day 21 (Phase 2)
Secondary outcome [3] 0 0
Phase 2 Safety: Number of Subjects Reporting Adverse Events - Dose limiting toxicity (DLT): An event is considered a DLT if it had a reasonable causal relationship to study drug & occurs within first 3 weeks of therapy & met at least one of the following criteria:
Grade 3 or 4 non-hematologic toxicity as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0, 2009 [NCI, 2009] with the exceptions of Grade 3 electrolyte disturbances that respond to correction within 24 hours; or Grade 3 rash, diarrhea, nausea, vomiting and mucositis that responded to standard medical supportive care within 48 hours).
Grade 4 neutropenia lasting =5 days
Febrile neutropenia
Grade 3 thrombocytopenia with bleeding
Grade 4 thrombocytopenia
Grade 4 anemia
Treatment delay of >14 days due to unresolved toxicity
Alanine aminotransferase (ALT) >3 times upper limit of normal (ULN) with bilirubin >2 times ULN
Timepoint [3] 0 0
Up to Day 51
Secondary outcome [4] 0 0
Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125 - RR is defined by the percentage of subjects with investigator-assessed Partial Cancer Antigen (CA) 125 Response (PR) or Complete CA 125 Response (CR) at any time during the study by GCIG CA 125. PR is greater than (>) 50% decrease in CA-125 values from baseline and no clinical or radiological evidence of new lesions. CR is decrease in the CA-125 to within the normal limits and less than (<) 40 IU/mL and no clinical or radiological evidence of disease.
Timepoint [4] 0 0
From Month 1 to 6
Secondary outcome [5] 0 0
Progression Free Survival (PFS) by RECIST or Clinical Symptomatic Progression of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A) - PFS was defined as the number of months between date of first GSK2110183 treatment and the earliest date of disease progression by RECIST or clinical symptomatic progression or death due to any cause whichever is earlier. Progression is defined using RECIST version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesion in reference to the smallest sum of the longest diameter recorded since the treatment started.
Timepoint [5] 0 0
From first dose until disease progression or death (approximately 36 months)
Secondary outcome [6] 0 0
PFS by RECIST of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A) - PFS was defined as the number of months between date of first GSK2110183 treatment and the earliest date of disease progression by RECIST or death due to any cause whichever is earlier. Progression is defined using RECIST version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesion in reference to the smallest sum of the longest diameter recorded since the treatment started.
Timepoint [6] 0 0
From first dose until disease progression or death (approximately 36 months)

Eligibility
Key inclusion criteria
Phase I

- 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

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
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [3] 0 0
Western Hospital - Footscray
Recruitment hospital [4] 0 0
Royal Women's Hospital - Parkville
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
8006 - East Melbourne
Recruitment postcode(s) [3] 0 0
3011 - Footscray
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Russian Federation
State/province [1] 0 0
Omskaya
Country [2] 0 0
Russian Federation
State/province [2] 0 0
Saint-Petersburg
Country [3] 0 0
United Kingdom
State/province [3] 0 0
London
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Surry

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Accenture
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01653912
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Richard A Brigandi, MD, PhD, FAAP
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications