Phase I/II study to investigate the safety, tolerability, efficacy and pharmacokinetics of ZK 219477 in combination with cisplatin as first-line therapy in chemotherapy-naive patients with extensive-disease (ED) stage small-cell lung cancer (SCLC)

• Register: EUCTR
• Last refreshed on: 28 January 2013
• Main ID: EUCTR2006-000067-29-DE
• Date of registration: 23/02/2007
• Prospective Registration: No
• Primary sponsor: Bayer Schering Pharma AG
• Public title: Phase I/II study to investigate the safety, tolerability, efficacy and pharmacokinetics of ZK 219477 in combination with cisplatin as first-line therapy in chemotherapy-naive patients with extensive-disease (ED) stage small-cell lung cancer (SCLC)
• Scientific title: Phase I/II study to investigate the safety, tolerability, efficacy and pharmacokinetics of ZK 219477 in combination with cisplatin as first-line therapy in chemotherapy-naive patients with extensive-disease (ED) stage small-cell lung cancer (SCLC)
• Date of first enrolment: 04/07/2006
• Target sample size: 52
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000067-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet the following criteria to enroll in this study:

1. Males or females aged > 18 years

2. Histologically or cytologically proven SCLC

3. Stage of extensive disease defined by the presence of distant metastases

4. At least 1 unidimensionally measurable lesion (suitable for modRECIST
evaluation)

5. WHO performance status 0 to 1

6. Adequate function of major organs and systems

• Hematopoietic:
- Hemoglobin >10 g/dL
- WBC:> 3.0 x 109/L
- Absolute neutrophil count: >1.5 x 109/L
- Platelet count: >100 x 109/L

• Hepatic:
- Total bilirubin: within normal range (< 1.5 times the upper limit of normal in
case of liver metastases)
- AST/ALT:< 2.5 times the upper limit of normal (< 5 times the upper limit of
normal in case of liver metastases)

• Renal:
- Creatinine: <1.5 times the upper limit of normal
- Creatinine clearance: > 60 ml/min

• Cardiovascular:No symptomatic congestive heart failure
- No unstable angina pectoris
- No myocardial infarction < 6 months prior to randomization
- No arrhythmia needing continuous treatment

• Nervous system:
- No Grade 2 or greater peripheral neuropathy

• Ear:
- No Grade 2 or greater hearing impairment

• No other uncontrolled concurrent illness

• No active infection

7. Survival expectation of at least three months

8. Negative pregnancy test at enrollment (females of childbearing potential only)

9. Agreement to use a highly effective method of birth control for adults of
reproductive potential

10. Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
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

Exclusion criteria:
Patients must not be enrolled if they meet any of the following criteria:

1. Prior chemotherapy for SCLC

2. Prior surgical resection for SCLC within 4 weeks prior to inclusion. Patient must
have recovered from all therapy related toxicities.

3. Prior radiotherapy for SCLC with the exception of radiation of brain metastases.
At least 3 weeks must have elapsed since radiotherapy and patient must have
recovered from all therapy related toxicities; the site of previous radiotherapy
should have evidence of progressive disease if it is the only site of disease.

4. Superior vena cava syndrome or obstruction of any vital structure

5. Untreated malignant hypercalcemia

6. Extensive disease amenable to radiation therapy

7. Symptomatic brain metastases requiring whole-brain irradiation (please note:
patients with brain metastases not requiring whole brain irradiation can be
enrolled)

8. History of another primary malignancy within the last 5 years with the exceptions
of non-melanoma skin cancer and carcinoma in situ of the cervix

9. Known allergy or hypersensitivity to platinum-containing drugs

10. Pregnant or breast-feeding women

11. Any condition that in the opinion of the investigator could hamper the compliance
with the study protocol

12. Use of any investigational drug within 4 weeks before start of study treatment
or inadequate recovery from any toxic effects of such therapy



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Extensive disease (ED) stage small-cell lung cancer (SCLC)

Intervention(s)

Product Code: ZK 00219477
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: not available
Current Sponsor code: ZK 219477
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10,5-

Pharmaceutical Form: Solution for infusion
INN or Proposed INN: cisplatin

Primary Outcome(s)

Secondary Objective: Phase I-part:
To investigate the pharmacokinetics of ZK 2194777 and cisplatin when given as a combination

To evaluate the anti-tumor activity of ZK 219477 in combination with cisplatin in patients with chemotherapy-naive, extensive-disease stage small cell lung cancer

Phase II-part:
To investigate the safety and tolerability of ZK 219477 in combination with cisplatin in this patient population

To evaluate the population pharmacokinetics of ZK 219477 and cisplatin

Main Objective: Phase I-part:
To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of ZK 219477 in combination with cisplatin

To investigate the safety and tolerability of ZK 219477 in combination with cisplatin

Phase II-part:
To evaluate the anti-tumor activity of ZK 219477 in combination with cisplatin in patients with chemotherapy-naive, extensive-disease stage small cell lung cancer

Primary end point(s): Proportion of patients with either complete response (CR) or partial response (PR) as "best overall response"

Secondary ID(s)

310101