Clinical Trials Register

Summary
EudraCT Number:	2012-001576-12
Sponsor's Protocol Code Number:	SGI-110-02
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-02-11
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-001576-12

A.3

Full title of the trial

A Randomized, Controlled, Open-Label, Phase 2 Trial of SGI-110 and Carboplatin in Subjects with Platinum-Resistant Recurrent Ovarian Cancer

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study of SGI-110 in people with recurrent ovarian cancer who are also resistant to platinum treatment.

A.4.1

Sponsor's protocol code number

SGI-110-02

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Astex Pharmaceuticals Inc
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Astex Pharmaceuticals Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medpace
B.5.2	Functional name of contact point	J L Cutter
B.5.3	Address:
B.5.3.1	Street Address	5375 Medpace Way
B.5.3.2	Town/ city	Cincinnati, OH
B.5.3.3	Post code	45227
B.5.3.4	Country	United States
B.5.4	Telephone number	0015135799911
B.5.6	E-mail	j.cutter@medpace.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	SGI-110
D.3.4	Pharmaceutical form	Lyophilisate and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SGI 110
D.3.9.2	Current sponsor code	SGI 110
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	carboplatin
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	carboplatin
D.3.9.3	Other descriptive name	CARBOPLATIN
D.3.9.4	EV Substance Code	SUB06614MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Platinum-Resistant Recurrent Ovarian Cancer

E.1.1.1

Medical condition in easily understood language

Ovarian Cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	PT
E.1.2	Classification code	10066697
E.1.2	Term	Ovarian cancer recurrent
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Stage 1
To assess the safety and tolerability of SGI-110+carboplatin and determine the maximum tolerated dose (MTD) for Stage 2

Stage 2
To assess and compare progression free survival (PFS) between SGI-110+carboplatin and Treatment Choice (TC) arms

E.2.2

Secondary objectives of the trial

Stage 1
• To determinethe objective response rate (ORR) based on both measurable disease and detectable disease
• To assess PFS at 6 months
To detemine:
• the clinical benefit rate (CBR)
• the duration of response (DOR)
• CA-125 reduction by ≥ 50%
• overall survival (OS)
• the pharmacokinetics (PK) of SGI-110 and decitabine in subjects with ovarian cancer, and determine if there is a PK interaction between SGI-110 and carboplatin

Stage 2
• To determine and compare the ORR for SGI 110+carboplatin and TC arms based on both measurable disease and detectable disease
• To assess and compare PFS at 6 months for SGI-110+carboplatin and TC arms
To detemine and compare:
• the CBR for SGI-110+carboplatin and TC arms
• the DOR for SGI-110+carboplatin and TC arms
• CA-125 reduction by ≥ 50% for SGI-110+carboplatin and TC arms
• OS for SGI-110+carboplatin and TC arms
• To determine the ORR for subjects in the TC arm who cross over to the SGI-110+carboplatin arm

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects who are women 18 years of age or older.
2. Subjects who have histologically or cytologically confirmed recurrent high-grade serous, endometriod, mixed cell, or clear cell epithelial ovarian cancer (Grade 2 or 3); primary peritoneal carcinomatosis; or fallopian tube cancer.
3. Subjects who have platinum-resistant disease (defined as having relapsed within 6 months of her last platinum-containing regimen). There is no limit on the number of prior treatment regimens.
4. Subjects must have had prior paclitaxel treatment.
5. Subjects who have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or detectable disease.
A. Detectable disease is defined in a subject as one who does not have measurable disease but has baseline values of CA-125 at least twice the upper limit of normal (ULN) and has at least one of the following conditions: (1) ascites and/or pleural effusion attributed to tumor or (2) solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST definitions for target lesions.
6. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Subjects with acceptable organ function, as evidenced by laboratory data:
A. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN or ≤ 5 times in the presence of liver metastases.
B. Total serum bilirubin ≤ 1.5 X ULN
C. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
D. Platelet count ≥ 100,000 cells/mm3
E. Serum creatinine levels ≤ 1.5 X ULN and calculated (by Cockcroft-Gault formula) or measured creatinine clearance ≥ 50 mL/min
8. Subjects must be at least 3 weeks from last chemotherapy. For all prior anticancer treatment including radiotherapy or targeted agents or hormonal therapy, a duration of more than 5 half-lives of the targeted/hormonal agents used must have elapsed and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria.
9. Subjects with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months following the last dose of study drug. Effective contraception includes methods such as oral contraceptives, double-barrier method (condom plus spermicide or diaphragm) or abstaining from sexual intercourse.
10. Subjects who sign an approved informed consent form for the study.
11. Subjects who are willing and able to comply with the protocol and study procedures including willingness to undergo tumor biopsy according to institutional standards (guided visually or by computed tomography [CT] or ultrasound), paracentesis, or thoracentesis for tumor cells before therapy at screening, and post-treatment (Cycle 2 Day 8 before carboplatin dose) if this is clinically and safely feasible to do so. In addition, any subject who has a therapeutic paracentesis or thoracentesis while on study should have tumor cells collected for analysis as part of the study whenever possible.

E.4

Principal exclusion criteria

1. Subjects who have hypersensitivity to SGI-110 and/or carboplatin or other components of these drug products; however, if the subject had a previous platinum hypersensitivity reaction, Investigator discretion may be used to enroll subjects who successfully undergo the institutional desensitization protocol.
2. Subjects who have received prior therapy with the hypomethylating agents azacitidine (Vidaza®) or decitabine (Dacogen®).
3. Subjects who are refractory to platinum treatment i.e., defined as having never responded to any prior platinum treatment.
4. Subjects who are a poor medical risk because of other systemic diseases or active uncontrolled infections.
5. Subjects with a life-threatening illness, medical condition or organ system dysfunction, or other reasons which, in the Investigator’s opinion, could compromise the subject’s safety, interfere with or compromise the integrity of the study outcomes including incomplete recovery from the acute effects from any prior anti-neoplastic therapy.
6. Subject must not have received mouse antibodies within 28 days of treatment.
7. Subjects with abnormal left ventricular ejection fraction (<50%) on echocardiogram or multiple-gated acquisition scan (MUGA).
8. Subject with Grade 2 or greater neuropathy.
9. Subjects with known brain metastases.
10. Subjects with prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least three years.
11. Subject with known history of human immunodeficiency virus (HIV) or if known seropositive for hepatitis C virus (HCV) or hepatitis B virus (HBV).

E.5 End points

E.5.1

Primary end point(s)

Stage 1:
• Incidence of DLTs and other adverse events to determine the MTD for Stage 2
Stage 2:
• Progression free survival (PFS) between SGI-110+carboplatin and TC arms

E.5.1.1

Timepoint(s) of evaluation of this end point

Stage 1
Safety assessment will be at visits that occur on every treatment day and also on Day 15 for all cycles in Stage 1 except in Cycle 1 where an additional safety visit on Day 22 is also required.

Stage 2
Measurable disease according to RECIST v1.1 or detectable disease will be assessed at baseline and after every other cycle (every 8 weeks) for 6 cycles then every 3 months thereafter until clinical and/or radiographic disease progression.

E.5.2

Secondary end point(s)

Stage 1:
• Objective response rate (ORR) defined as CR+PR based on both measurable disease and detectable disease
• PFS at 6 months
• Clinical benefit rate (CBR) defined as CR+PR+SD for at least 3 months
• Percentage of subjects with CA-125 reduction by ≥ 50%
• Duration of response (DOR)
• Overall survival (OS)
• Cmax, Cmin, AUC and other secondary PK parameters of SGI-110, decitabine and carboplatin in all subjects during Cycle 1
Stage 2:
• ORR defined as CR+PR for SGI-110+carboplatin and TC arms based on both measurable disease and detectable disease
• PFS at 6 months for SGI-110+carboplatin and TC arms
• CBR defined as CR+PR+SD for at least 3 months for SGI-110+carboplatin and TC arms
• Percentage of subjects with CA-125 reduction by ≥ 50% for SGI-110+carboplatin and TC arms
• DOR for SGI-110+carboplatin and TC arms
• OS for SGI-110+carboplatin and TC arms
• ORR for TC subjects who cross over to SGI-110+carboplatin

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy:
baseline and after every other cycle (every 8 weeks) for 6 cycles then every 3 months until clinical and/or radiographic disease progression.
CA-125 at baseline and after every cycle.
PK:
Stage 1
SGI-110 and decitabine: Cycle 1, Day 1: pre-dose, 15 min, 30 min, 60 min, 90 min and 2 hr, 4 hr, 6 hr and 8 hr post-dose.
Carboplatin: Cycle 1, Day 8: pre-dose, 30 min into the IV-infusion, 60 min (coincide with the end infusion), then 30-min, 1 hr, 2 hr, 4 hr, and 7-8 hrs after the end of carboplatin IV infusion.

Safety: every treatment day and Day 8, 15 and 22 for all cycles in Stage 1 and 2.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

110

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

none

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-03-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-04-15

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