Clinical Trials Register

Summary
EudraCT Number:	2011-001084-42
Sponsor's Protocol Code Number:	9090-08
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-05-19
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

2011-001084-42

A.3

Full title of the trial

A Randomized, Phase IIb/III Study of Ganetespib (STA-9090) in Combination with Docetaxel versus Docetaxel alone in Subjects with Stage IIIb or IV Non-Small Cell Lung Cancer

A.3.1

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

A study to assess the effect of Ganetespib (study drug) in combination with Docetaxel versus Docetaxel alone in patients with advanced Non-Small Cell Lung Cancer

A.4.1

Sponsor's protocol code number

9090-08

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	Synta Pharmaceuticals Corp.
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	Synta Pharmaceutical Corp
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	Synta Pharmaceuticals Corp.
B.5.2	Functional name of contact point	Senior Clinical Trials Manager
B.5.3	Address:
B.5.3.1	Street Address	45 Hartwell Avenue
B.5.3.2	Town/ city	Lexington
B.5.3.3	Post code	MA 02421
B.5.3.4	Country	United States
B.5.4	Telephone number	001781541 7180
B.5.5	Fax number	001781541 7141
B.5.6	E-mail	AGupta@syntapharma.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.3.1	Product name	ganetespib
D.3.2	Product code	STA-9090
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	ganetespib
D.3.9.1	CAS number	888216-25-9
D.3.9.2	Current sponsor code	STA-9090
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	25
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

Non-Small Cell Lung Cancer

E.1.1.1

Medical condition in easily understood language

Lung 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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10025054
E.1.2	Term	Lung cancer non-small cell stage IIIB
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10025055
E.1.2	Term	Lung cancer non-small cell stage IV
E.1.2	System Organ Class	100000004864

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
Evaluate progression free survival (PFS) in subjects with NSCLC with adenocarcinoma histology who present with elevated baseline total LDH treated with the combination of ganetespib and docetaxel compared to docetaxel alone.

Evaluate PFS in subjects with KRAS mutated NSCLC.

Stage 2
Assess OS in subjects with stage IIIB or IV NSCLC treated with the combination of ganetespib and docetaxel compared to docetaxel alone

E.2.2

Secondary objectives of the trial

Stage 1
•Evaluate the PFS & OS in subjects with NSCLC with adenocarcinoma histology
•Compare the two treatments in subjects with elevated baseline serum levels of total LDH with respect to the following: Overall Response Rate (ORR), Disease Control Rate (DCR), tumor size change, 1-year OS rate, and OS
•Compare the two treatments in subjects with mutated KRAS (mKRAS) with respect to the following: ORR, DCR, tumor size change, 1-year OS rate, and OS
•Compare the two treatment groups in the adeno population with respect to the following: ORR, DCR, tumor size change and 1-year OS rate
•Compare the two treatment groups with respect to other important pre-specified prognostic factors according to the following: PFS, ORR, DCR, tumor size change, 1-year OS rate, and OS

Stage 2
1. Compare the two treatment groups with respect to the following: PFS, ORR, DCR, tumor size change and 1-year OS

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female subjects aged 18 years or older
2. Pathologically confirmed (by histology or cytology) diagnosis of NSCLC with predominantly adenocarcinoma histology
3. Stage IIIB or IV NSCLC according to the AJCC Cancer Staging Manual 7th Edition 2010
4. ECOG Performance Status 0 or 1 and life expectancy of at least 3 months at screening
5. Eligible for second-line systemic therapy:
•Patients must have received no more than one prior therapy (first-line therapy) for advanced disease (Stage IIIB or IV). Prior first-line therapy may include:
i. A platinum-based chemotherapy doublet (with or without biological agents); or
ii. EGFR tyrosine kinase inhibitors (TKIs) for EGFR-mutated disease
•NOTE: Maintenance therapy following first-line treatment for advanced disease is allowed, as long as it was started no more than 4 weeks after the last dose of first-line therapy
•NOTE: Previous anticancer treatment must have stopped at least 2 weeks prior to randomization
6. Measurable disease by modified RECIST 1.1
7. Radiologic evidence of primary or secondary disease progression following first-line treatment.
Disease progression is defined as:
•Appearance of any new lesion or any measureable increase of one or more existing lesions. Radiological scans or radiology reports from the subject’s most recent treatment must document the baseline or lowest tumor burden (nadir scans) and disease progression.
NOTE: Disease progression is defined either as a primary progression where a patient never responded to first line treatment; or secondary progression, where disease progression occurred after initial response
8. Subjects with CNS metastases are eligible, provided that the CNS metastases are radiologically and clinically stable for at least 4 weeks after appropriate therapy (with or without steroid treatment) prior to randomization
9. Adequate hematologic function defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Hemoglobin ≥ 9 g/dL
• Platelets ≥ 100 × 109/L
10. Adequate hepatic function defined as:
• Albumin ≥3 g/dL
• Serum total bilirubin ≤1.5 x ULN
• AST and ALT ≤1.5 × ULN without liver metastases; ≤5 × ULN if documented liver metastases
11. Adequate renal function defined as
• Serum Creatinine ≤1.2 mg/dL or calculated creatinine clearance (CLcr) per Cockgroft- Gault formula ≥ 50mL/min
12. Negative serum pregnancy test at study entry for female subjects of childbearing potential
13. Female subjects of childbearing potential and males must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and for 30 days after the last dose of study drug.
14. Ability to understand, and willingness to sign, a written informed consent document and to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
15. Translational Research: archived or newly obtained tumor tissue, consisting of at least 10 unstained slides or a block of fixed tumor tissue, must be collected prior to randomization

E.4

Principal exclusion criteria

1. Presence of active or untreated CNS metastases as determined by MRI or CT scan performed during screening.
2. Active malignancies other than NSCLC within the last 5 years with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin
3. Serious cardiac illness or medical conditions including but not confined to:
• History of documented congestive heart failure (CHF), New York Heart Association
class II/III/IV, with a history of dyspnea, orthopnea or edema that requires current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics. NOTE: Use of these medications for the treatment of hypertension is allowed
• Baseline QTc > 470 msec or history of QT prolongation while taking other medications
• High-risk uncontrolled arrhythmias (ventricular tachycardia, high-Grade AV-block, supra-ventricular arrhythmias which are not adequately rate-controlled) that require current treatment with the following anti-arrythmic drugs: flecainide, moricizine or propafenone
• Current coronary artery disease with a history of myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery
4. Radiotherapy within 2 weeks prior to randomization (related toxicities must be ≤Grade 1)
5. Prior radiotherapy to the only area of measurable disease
6. Major surgery (unrelated to NSCLC) within 4 weeks prior to randomization
7. Hemoptysis ≥ Grade 2 at randomization
8. Peripheral neuropathy ≥ Grade 2 at randomization
9. History of severe allergic or hypersensitivity reactions to docetaxel or excipients (eg,
polyethylene glycol [PEG] 300 and polysorbate 80)
10. Women who are pregnant or lactating
11. Significant weight loss of ≥ 10% body weight within the 4 weeks prior to randomization

E.5 End points

E.5.1

Primary end point(s)

Stage 1
The primary endpoints of the study are (1) PFS in adenocarcinoma histology subjects with elevated baseline total LDH and (2) PFS in a subset of subjects with KRAS mutated disease.

Stage 2
Evaluation of OS in the two treatment arms

E.5.1.1

Timepoint(s) of evaluation of this end point

Stage 1
The primary analysis of PFS in adenocarcinoma subjects with elevated baseline serum LDH will be conducted when approximately 73 PFS events have been observed in this subgroup. The primary analysis of PFS in subjects with KRAS mutation will be conducted when approximately 73 PFS events have occurred in this population. This analysis will include all subjects with KRAS mutation enrolled in the study

Stage 2
A formal interim OS analysis is planned when approximately 125 OS events (approximately 40% of the total number of deaths) have been observed.
The primary analysis for median OS will be conducted when approximately 311 OS events have been observed.

E.5.2

Secondary end point(s)

Stage 1
Overall Response Rate, Disease Control Rate, tumour size change, and 1 year overall survival and overall survival between the 2 treatment groups.
Stage 2
Progression Free Survival, Overall Response Rate, Disease Control Rate, tumour size changes, and 1 year overall survival and overall survival between the 2 treatment groups

E.5.2.1

Timepoint(s) of evaluation of this end point

Stage 1 and Stage 2
Tumor size changes from baseline to at least 6 or 12 weeks
Disease Control Rate is defined as the proportion of patients with best response, according to modified RECIST 1.1, of CR, PR or SD, where the SD must be for at least 6 weeks (DCR-6) or 12 weeks (DCR-12)

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

Yes

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

Yes

E.6.11

Pharmacogenomic

Yes

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)

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

IMP as an add-on to standard of care treatment

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Belgium

Bosnia and Herzegovina

Canada

Czech Republic

Germany

Hungary

Netherlands

Poland

Romania

Russian Federation

Serbia

Spain

Ukraine

United Kingdom

United States

Croatia

E.8.7

Trial has a data monitoring committee

Yes

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

End of trial is last survival follow-up which is approx 6 to 12 months after last patients' last visit

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

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:

540

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

360

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

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

440

F.4.2.2

In the whole clinical trial

900

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)

Patients should follow normal standard of care for treatment.

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

2011-07-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-08-02

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-11-04

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