Clinical Trials Register

Summary
EudraCT Number:	2004-000330-36
Sponsor's Protocol Code Number:	TLK286.3020
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-04-13
Trial 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

Spain - AEMPS

A.2

EudraCT number

2004-000330-36

A.3

Full title of the trial

Phase 3 Randomized Study of TLK286 (Telcyta?) versus Gefitinib (Iressa®) as Third-Line Therapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Ensayo fase III, aleatorizado, de TLK286 versus Gefitiniv (Iressa®) como tercera linea de tratamiento en el cáncer de pulmón no microcítico metastásico o localmente avanzado

A.3.1

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

A Clinical Trial to Compare the Effectiveness of TLK286 (Telcyta?) and Gefitinib (Iressa®) in Non-Small Cell Lung Cancer

A.3.2

Name or abbreviated title of the trial where available

ASSIST-2

A.4.1

Sponsor's protocol code number

TLK286.3020

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00080340

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	Telik, 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	Telik, 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	Telik, Inc.
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	700 Hansen Way
B.5.3.2	Town/ city	Palo Alto, CA
B.5.3.3	Post code	94304-1016
B.5.3.4	Country	United States
B.5.4	Telephone number	1650845-7700
B.5.5	Fax number	1650845-7794
B.5.6	E-mail	clinicaltrials@telik.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	canfosfamide HCl for injection
D.3.2	Product code	TLK286
D.3.4	Pharmaceutical form	Lyophilisate 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	canfosfamide HCl
D.3.9.1	CAS number	439943-59-6
D.3.9.2	Current sponsor code	TLK286
D.3.9.3	Other descriptive name	Telcyta
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	265
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	Comparator
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	gefitinib
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GEFITINIB
D.3.9.1	CAS number	184475-35-2
D.3.9.2	Current sponsor code	ZD1839
D.3.9.3	Other descriptive name	Iressa
D.3.9.4	EV Substance Code	SUB20637
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	250
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, including squamous cell carcinoma, undifferentiated carcinoma, adenocarcinoma, mixed (adenocarcinoma with squamous cell carcinoma) or large cell carcinoma, recurrent or resistant following two prior chemotherapy regimens which must have included a platinum agent (carboplatin or cisplatin).

E.1.1.1

Medical condition in easily understood language

Non-small cell lung cancer, recurrent or resistant after two prior chemotherapy treatments.

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	PT
E.1.2	Classification code	10059515
E.1.2	Term	Non-small cell lung cancer metastatic
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	PT
E.1.2	Classification code	10029522
E.1.2	Term	Non-small cell lung cancer stage IV
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	PT
E.1.2	Classification code	10029521
E.1.2	Term	Non-small cell lung cancer 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	PT
E.1.2	Classification code	10029515
E.1.2	Term	Non-small cell lung 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

To demonstrate superiority in survival in favor of TLK286 as compared to active control therapy with gefitinib in the intent-to-treat (ITT) population

E.2.2

Secondary objectives of the trial

1. To evaluate and compare the safety profile of each treatment arm

2. To demonstrate superiority in time to tumor progression (TTP) in favor of TLK286 as compared to active control therapy with gefitinib

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A subgroup analysis is planned to be performed on patients with non-adenocarcinoma histiologic cell types as defined as ?other cell types? including squamous cell, undifferentiated, mixed, and large cell. Both survival and TTP will be examined in this subset of patients.

E.3

Principal inclusion criteria

1. Histologically confirmed non-small cell lung cancer, including squamous cell carcinoma, undifferentiated carcinoma, adenocarcinoma, mixed (adenocarcinoma with squamous cell carcinoma) or large cell carcinoma. Patients with mixed tumors containing small cell lung carcinoma elements, bronchoalveolar elements or pure bronchoalveolar subtype of adenocarcinoma are not eligible.

2. Stage III or IV disease not curable with surgery, radiation or combined modality therapy at study entry

3. Recurrent or resistant disease following two prior chemotherapy regimens which must have included a platinum agent (carboplatin or cisplatin), [e.g. Patients must have received treatment with a platinum agent (carboplatin or cisplatin) as neoadjuvant or adjuvant therapy in combination with surgery; as treatment for metastatic disease; or in combined modality chemoradiation for stage III disease.]

4. Measurable disease according to RECIST criteria, with documented tumor progression. Pleural effusions, ascites, osseous metastases, and lesions located in previously irradiated areas are not considered measurable.

5. Eastern Co-Operative Group (ECOG) performance status of 0?2

6. ? 18 years of age

7. Adequate liver and renal function as evidenced by the following:
? Creatinine ? 2.0 mg/dL or calculated creatinine clearance of at least 60 mL/min by Cockcroft-Gault Equation
? Total bilirubin ? 2.0 mg/dL (except when Gilbert syndrome is clearly documented and other LFTs are normal)
? ALT ? 3 x the upper limit of normal (ULN). If the patient has hepatic metastases, then ALT ? 5 x the ULN
? Alkaline phosphatase ? 5 x the ULN (except when bone metastases are present in the absence of any liver disorders)
? Albumin ? 3.0 g/dL

8. Adequate bone marrow reserve as indicated by:
? ANC ? 1,500 cells/mm3
? Platelet count ? 100,000 cells/mm3
? Hemoglobin ? 9.0 g/dL

9. Willing and able to comply with the protocol for the duration of the study

10. Written informed consent given prior to any study-specific screening procedures

11. Women and men of child-bearing potential enrolled in the study must agree to practice an effective method of birth control during the study and for at least six months after receiving their last study treatment

E.4

Principal exclusion criteria

1. Treatment with more than two prior chemotherapy regimens

2. Histologically confirmed mixed tumors containing small cell lung carcinoma elements, bronchoalveolar elements, or pure bronchoalveolar subtype of adenocarcinoma

3. Treatment with chemotherapy or radiotherapy (except limited in nature) within three weeks of study entry or failure to recover from the toxic effects of any of these therapies within six weeks prior to study entry

4. History of bone marrow transplantation or stem cell support

5. Leptomeningeal metastases or carcinomatous meningitis

6. Known history of CNS metastasis are ineligible unless the patient has had treatment with surgery or radiation therapy, is neurologically stable, does not require oral or intravenous steroids or anticonvulsants

7. A history of prior malignancy except for adequately treated carcinoma in situ of the uterine cervix, incidental endometrial cancer Stage I, basal cell or squamous cell skin cancer, or other cancer for which the patient has been disease-free for at least three years (e.g., bladder cancer, head and neck cancer). Patients with elevated PSA in the absence of known metastatic prostate cancer (even if there is previously treated prostate cancer) are eligible. These patients should be discussed with the medical monitor prior to study entry

8. Routine prophylactic use of G-CSF or GM-CSF within two weeks prior to study entry

9. Evidence of gross hematuria at the time of study entry

10. Uncontrolled hypercalcemia (serum calcium ? 11.0 mg/dL). Calcium should be corrected for serum albumin

11. Serious uncontrolled intercurrent infections (bacterial or viral) or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for study entry

12. History of uncontrolled seizures, CNS disorders, or psychiatric disability judged by the Investigator to be clinically significant, precluding informed consent or adversely affecting ability to comply with study procedures

13. Pregnant or lactating women and women of child-bearing potential not using a reliable and appropriate contraceptive method. Postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-child-bearing potential.

14. Failure to recover from any prior surgery, or major surgery within three weeks of study entry (other than a minor biopsy or placement of a venous access device)

15. Grade 3 or 4 peripheral neuropathy

16. Known history of HIV positivity (regardless of immune status)

17. Weight loss ? 10% within six weeks prior to study entry

18. Uncontrolled pleural effusion (defined as requiring two or more thoracenteses within four weeks prior to study entry)

19. Known history of prior TLK286 therapy

20. Known history of prior gefitinib therapy

E.5 End points

E.5.1

Primary end point(s)

The final analysis will be performed when 415 deaths have been observed. Kaplan-Meier curves will be performed for patient overall survival, median survival, and time to tumor progression, including quartiles for each variable. Kaplan-Meier analysis will be done using PROC LIFETEST in Statistical Analysis System® (SAS). Other analyses will be conducted as necessary.

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

Toxicity will be assessed by the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Version 2.0. Adverse events will be classified into body system categories based on MedDRA terminology. Adverse events will be graded by the Investigator using the following grading scale: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) or Grade 4 (life-threatening). The analysis will include listings with frequencies and severity of adverse events.

E.5.2.1

Timepoint(s) of evaluation of this end point

An independent DMC committee will be established by Telik, Inc. The responsibility of this committee will be to assess the results for the safety data in order to safeguard the interest of the study participants and to preserve the integrity and credibility of the trial. The DMC will recommend to the Telik, Inc. Steering Committee (TSC) whether to continue, modify or stop the study. Recommendations from the DMC regarding continuation or termination of the trial will be based on safety data.

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

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)

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)

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

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

Argentina

Australia

Belgium

Brazil

Chile

Germany

Italy

Russian Federation

Spain

United Kingdom

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 - Final analysis will be performed when 415 deaths have been observed.

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.1.1.1

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:

335

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

195

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

F.3.3.1

Women of childbearing potential not using contraception