Clinical Trials Register

Summary
EudraCT Number:	2009-012983-14
Sponsor's Protocol Code Number:	DMS32212R
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2009-12-17
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

Bulgarian Drug Agency

A.2

EudraCT number

2009-012983-14

A.3

Full title of the trial

Randomized, multicenter, double-blind, phase 3 trial of Tavocept versus Placebo in patients with newly diagnosed or relapsed advanced primary adenocarcinoma of the lung treated with docetaxel or paclitaxel plus cisplatin

Рандомизирано, многоцентрово, двойно сляпо, фаза 3 изпитване на тавосепт в сравнение с плацебо при пациенти с новодиагностициран или рецидивирал напреднал първичен аденокарцином на белия дроб, лекуван с доцетаксел или паклитаксел плюс цисплатин

A.4.1

Sponsor's protocol code number

DMS32212R

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	BioNumerik 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	BioNumerik 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
B.5.2	Functional name of contact point

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	Tavocept
D.3.2	Product code	BNP7787
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	16208-15-8
D.3.9.2	Current sponsor code	BNP7787
D.3.9.3	Other descriptive name	Disodium, dithio-bismercaptoethansulfonate; 2,2'-thio-bisethanesulphonic acid, disodium salt
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	200
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Newly diagnosed or relapsed advanced (Stage IIIB/IV) primary adenocarcinoma of the lung

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	PT
E.1.2	Classification code	10025031
E.1.2	Term	Lung adenocarcinoma
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 determine if co-administration of Tavocept (as compared to placebo control) with first-line combination chemotherapy (paclitaxel or docetaxel plus cisplatin) results in a significant increase in overall survival in the study-defined patient population.

E.2.2

Secondary objectives of the trial

To determine if Tavocept co-administration concurrently prevents and/or mitigates cisplatin-induced renal toxicity and other common and important chemotherapy-induced toxicities, including anemia and emesis in patients, and to determine if progression free survival improves.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with confirmed histopathological diagnosis of inoperable advanced (stage IV) primary adenocarcinoma (including bronchioalveolar cell carcinoma) of the lung. If pathological, or radiological findings are inconclusive for a diagnosis of primary adenocarcinoma of the lung, additional studies must be performed to confirm primary lung versus metastatic adenocarcinoma.
2. All patients must have documented Stage IV disease in accordance with the AJCC TNM staging system 7th edition (M1a=separate tumor nodule[s] in a contralateral lobe; tumor with pleural nodules or malignant pleural or pericardial effusion, M1b= distant metastases).
3. Patients may have newly diagnosed or recurrent/relapsed disease.
4. No form of any prior systemic treatment is allowed for non-small cell lung cancer, including chemotherapy, immunotherapy (e.g., monoclonal antibodies, vaccines), hormonal therapy (excluding dexamethasone or corticosteroids), targeted therapies (including EGFR inhibitors), or investigational drugs.
5. Prior radiation therapy is allowed, provided that at least one (1) area of measurable (by CT scan) or evaluable disease by RECIST (Version 1.1) that has not been subject to prior irradiation.
6. Prior prophylactic cranial irradiation (PCI) or radiation therapy is allowed provided that any such therapy is completed and any radiation-induced sequelae are recovered at least 21 days before randomization.
7. Patients with an ECOG performance status of 0 or 1.
8. Patients who are at least 18 years of age.
9. Patients with documented stable CNS metastases with no cognitive deficits, or progressive sensory or motor deficits or seizures during the last 21 days prior to randomization are eligible. Patients must have discontinued anti-seizure medications and steroids at least 21 days prior to patient randomization.
10. Patients must have fully recovered from any prior major surgical or diagnostic staging procedure (e.g., thoracotomy, mediastinoscopy), and have a post-operative status of at least 30 days before randomization.
11. Patients must have adequate bone marrow, adequate hepatic function, and a baseline creatinine levels documented by specific laboratory criteria within
21 days prior to randomization :
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 100 × 109/L
• Total bilirubin < the upper limit of normal (ULN)
• Aspartate aminotransferase (AST/SGOT) ≤ 1.5 × ULN
• Alanine aminotransferase (ALT/SGPT) ≤ 1.5 × ULN
• Alkaline phosphatase ≤ 2.5 × ULN
• Baseline serum creatinine level no greater than 1.5 mg/dL or 133 μmol/L.
• Creatinine clearance ≥ 60 mL/min, calculated using a modified Cockcroft-Gault formula2 (see Table 1 for the formula).
• Magnesium ≥ 1.7 mg/dL
12. Female patients of child-bearing potential must have a negative pregnancy test,
and must agree to use an acceptable contraceptive method during the study. Male
patients with partners of child-bearing potential must also agree to use an adequate
method of contraception.
13. Patients must have been disease-free at least 2 years for other malignancies,
excluding:
• Curatively-treated basal cell carcinoma,
• Squamous cell carcinoma of the skin, or
• Carcinoma in situ of the cervix.
14. Patients with prior surgical resection and no prior chemotherapy for
primary adenocarcinoma of the lung who have relapsed are allowed.
15. Provide written informed consent prior to any screening procedures

E.4

Principal exclusion criteria

1. Patients with small cell, squamous cell, large cell, undifferentiated, mesothelioma,
or any form of mixed (e.g., small cell and adenocarcinoma or squamous and
adenocarcinoma) histopathological diagnosis of primary lung cancer.
2. Patients who do not have documented Stage IV disease (in accordance with AJCC TNM staging system 7th edition).
3. Patients with metastatic adenocarcinoma arising from any primary site other than the lung.
4. Patients with recent onset (within 6 months of randomization) of congestive heart
failure (New York Heart Association Classification Class II or greater), angina
pectoris, unstable angina pectoris, uncontrolled ventricular tachycardia,
myocardial infarction, stroke, or transient ischemic attacks.
5. Patients with unstable CNS metastases (characterized by progressive
sensory/motor impairment, cognitive/speech impairment, or seizure activity)
within 21 days before randomization.
6. Patients who do not have at least one (1) measurable or non-measurable but
assessable disease site that has not been previously irradiated.
7. Patients who are known to be HIV-positive.
8. Patients with active infections, uncontrolled high blood pressure, uncontrolled
diabetes mellitus, uncontrolled seizures (not due to CNS metastases) within the
last 6 months, or other serious underlying medical condition.
9. Patients with documented hypersensitivity to any of the study medications or
supportive agents that may be used.
Patients who are pregnant or are breastfeeding.
11. Patients who have undergone blood transfusions within 10 days before
randomization.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is overall survival (OS); defined as the time period from the date of patient randomization to the date of death due to any cause.

E.5.1.1

Timepoint(s) of evaluation of this end point

The time period from the date of patient randomization to the date of death due to any cause

E.5.2

Secondary end point(s)

• Progression-Free Survival (PFS), defined as the time from the date of patient randomization to the date of first-documented tumor/disease progression using RECIST or death due to any cause.
•Proportion of patients having no impact of chemotherapy-induced emesis on daily life as measured by the Functional Living Index-Emesis. No impact on daily life is defined as an average score of > 6 on the seven-point scale.
•Incidence of a 30% or greater decrease in the calculated creatinine clearance relative to baseline calculated creatinine clearance.
•Incidence of NCI-CTCAE grade 2, 3, or 4 anemia (hemoglobin).

E.5.2.1

Timepoint(s) of evaluation of this end point

The time from the date of patient randomization to the date of first documented tumor/ disease progression using RECIST or death due to any cause

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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.8.3

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

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

Follow-up of all randomised patients until death

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