Clinical Trials Register

Summary
EudraCT Number:	2011-000201-44
Sponsor's Protocol Code Number:	IPI-504-14
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-07-21
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-000201-44

A.3

Full title of the trial

A Phase 2, Double-Blind, Placebo-Controlled Study of IPI-504 and Docetaxel in Previously Treated patients 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

Advanced Non-Small Cell Lung Cancer Trial

A.4.1

Sponsor's protocol code number

IPI-504-14

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	Infinity 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	Infinity 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	Infinity Pharmaceuticals, Inc
B.5.2	Functional name of contact point	IPI-504-14 Trial Information
B.5.3	Address:
B.5.3.1	Street Address	780 Memorial Drive
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	MA 02139
B.5.3.4	Country	United States
B.5.4	Telephone number	+1617453 1000
B.5.5	Fax number	+1617453 1001
B.5.6	E-mail	IPI-504-14@infi.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	IPI 504
D.3.2	Product code	IPI 504
D.3.4	Pharmaceutical form	Powder and solvent 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.3.9.1	CAS number	857402-63-2
D.3.9.2	Current sponsor code	IPI 504
D.3.9.3	Other descriptive name	Retaspimycin hydrochloride
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	844.5
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	Docetaxel
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	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
D.3.9.4	EV Substance Code	SUB12492MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	20 to 80
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Stage IIIB or IV Non-Small Cell Lung Cancer

E.1.1.1

Medical condition in easily understood language

Advanced Non-Small Cell 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	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The overall survival (OS) of patients with previously treated NSCLC administered IPI-504 plus docetaxel will be compared to patients treated with placebo plus docetaxel in all patients and patients with squamous cell carcinoma (determined by central histology review).

E.2.2

Secondary objectives of the trial

• To compare the PFS, TTP, and ORR of all patients and patients with squamous cell carcinoma administered IPI-504 plus docetaxel versus placebo plus docetaxel
• To compare the safety of IPI-504 plus docetaxel versus placebo plus docetaxel
• To investigate potential tissue, serum, and/or plasma biomarkers of the activity of IPI-504 plus docetaxel

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients must be ≥18 years of age or legal age of consent for the applicable country at the time of signing the Informed Consent Form (ICF).

• Patients must have NSCLC with both of the following characteristics:
- Pathologic confirmation
- Stage IIIB or IV

• Patients must have at least a ≥15 pack year smoking history and must have been an active smoker within 20 years of diagnosis. Number of pack years = (number of packs per day smoked) x (number of years as a smoker)

• Patients must have archival NSCLC tissue available to provide for analysis or agree to a biopsy of their NSCLC prior to study entry

• Patients must have received no more than 2 prior systemic therapy regimens (including chemotherapy alone, tyrosine kinase inhibitor therapy alone, investigational agents alone, or combination regimens) for Stage IIIb or IV disease.

• Patients must have measurable disease by RECIST 1.1 criteria. If the target lesion is in a prior irradiated field, it may be selected as long as there is documented progression (increase of 20% from baseline) either during or since radiation and the lesion is a minimum length of ≥10mm.

• Patients must have an ECOG performance status of 0 or 1

• Women of child-bearing potential (WCBP)

• All WCBP and all sexually active male patients must agree to use adequate methods of birth control throughout the study.

E.4

Principal exclusion criteria

• Prior docetaxel, IPI-504 or other Hsp90 inhibitor (e.g., 17-AAG, DMAG, STA-9090).

• Received any of the following treatments in the specified timeframe prior to first dose of any study medication (IPI-504/ placebo or docetaxel):
within 1 week with erlotinib or gefitinib
within 2 weeks with any other tyrosine kinase inhibitor (approved or investigational)
within 2 weeks with radiation therapy
within 4 weeks with any biologic therapy (antibody, vaccine, or other protein-based therapy)
within 4 weeks with any conventional chemotherapy
within 4 weeks with investigational drug, investigational device, or approved therapy used in an investigational manner
within 6 weeks with nitrosoureas or mitomycin C.

• Use of a medication or food that is a clinically relevant CYP3A inhibitor or inducer within 2 weeks prior to Cycle 1, Dose 1, with the exception of dexamethasone for docetaxel premedication.
Inadequate hematologic function defined as: absolute neutrophil count (ANC) <1,500 cells/mm3
platelet count <75,000 cells/mm3
hemoglobin <9.0 g/dL (may be increased to this level with transfusion as long as there is no evidence of active bleeding).

• Inadequate hepatic function defined by:

• AST and/or ALT >1.5 x ULN
• Total bilirubin >ULN (inclusion of patients with documented Gilbert’s syndrome may be discussed with Medical Monitor)
• Alkaline phosphatase >2.5 x ULN.Patients with elevated alkaline
phosphatase are eligible if they have either:
♦ No liver metastases or
♦ Alkaline phosphatase liver fraction ≤2.5X ULN or
♦ 5´ nucleotidase ≤2.5X ULN or
♦ GGT ≤2.5 x ULN.

• Inadequate renal function defined by serum creatinine >1.5 x ULN.

• Patients with clinically active brain metastases (e.g., requiring therapy with steroids or radiation therapy; or with intracranial progression 4 weeks after the completion of radiation therapy) or an uncontrolled seizure disorder, ongoing spinal cord compression, or carcinomatous meningitis. Patients with clinically stable brain metastases (previously treated or untreated) are eligible.

• Sinus bradycardia (resting heart rate <50 bpm). Patients with sinus bradycardia secondary to pharmacologic therapy may enroll if discontinuation of the therapy results in normalization of the resting heart rate to within normal limits.

• Significant cardiac disease

• Previous or current malignancies at other sites within the last 2 years, with exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, or prostate cancer that does not require active treatment per National Comprehensive Cancer Network (NCCN) guidelines. Patients with localized prostate cancer with a Gleason score of 6 or less should be followed by active surveillance and are eligible for this study.

• Prior hepatic resections or hepatic-directed therapy (e.g., chemoembolization or Theresphere®).

• Known HIV-positive patients receiving combination antiretroviral therapy.

• Women who are pregnant or lactating.

• Any other condition that, in the opinion of the Investigator, may compromise the safety (including but not limited to active hepatitis or liver cirrhosis), compliance of the patient, or would preclude the patient from successful completion of the study.

• Grade 3 or 4 thromboembolic event within 1 month, unless on a stable dose of anticoagulant.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is Overall Survival, defined as time from randomization to death due to any cause.

E.5.1.1

Timepoint(s) of evaluation of this end point

Q4 2013

E.5.2

Secondary end point(s)

• ORR, defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Criteria in Solid Tumors (RECIST 1.1).

• PFS, defined as time from randomization to disease progression or death whichever occurs first.

• TTP, defined as time from randomization to disease progression (per RECIST 1.1)

• Incidence of adverse events (AEs)
• Incidence of serious adverse events (SAEs)
• Laboratory test results
• Vital sign results

E.5.2.1

Timepoint(s) of evaluation of this end point

Final Q4 2013

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

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

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

Korea, Republic of

Russian Federation

Taiwan

United States

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

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

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