International, randomized, open-label, Phase 3 trial of gemcitabine/cisplatin plus PF-3512676 versus gemcitabine/cisplatin alone as first-line treatment of patients with advanced non-small cell lung cancer

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2005-004557-10-GB
• Date of registration: 28/10/2005
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc
• Public title: International, randomized, open-label, Phase 3 trial of gemcitabine/cisplatin plus PF-3512676 versus gemcitabine/cisplatin alone as first-line treatment of patients with advanced non-small cell lung cancer
• Scientific title: International, randomized, open-label, Phase 3 trial of gemcitabine/cisplatin plus PF-3512676 versus gemcitabine/cisplatin alone as first-line treatment of patients with advanced non-small cell lung cancer
• Date of first enrolment: 21/02/2006
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004557-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: gemcitabine/cisplatin chemotherapy alone

Countries of recruitment

Belgium, Czech Republic, Germany, Hungary, Italy, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
Cytologic specimens for diagnosis or for cell type classification must have been obtained from bronchial brushings or washings or from needle aspiration of a defined lesion. Sputum cytology alone will not be acceptable for diagnosis or for cell type classification.

2. Advanced NSCLC with documented AJCC Stage IIIB (with pleural effusion) or Stage IV disease.

3. Measurable disease defined by at least one lesion that can be accurately measured in at least one dimension as >=20 mm with conventional techniques or >=10 mm with spiral CT scan within 28 days prior to the planned start of study treatment (RECIST criteria). Note: Prior radiation to the only site of measurable disease will deem the patient ineligible unless progression is documented at the site after completion of radiation.

4. No prior systemic treatment for NSCLC with chemotherapy, immunotherapy, biologic response modifiers or other investigational drugs.

5. Prior surgery or radiation therapy is permitted if completed at least 3 weeks prior to enrollment and all acute toxicities have resolved to baseline or to CTC Grade 1 (NCI CTCAE v3.0)

6. Males or females aged >=18 years

7. ECOG performance status (PS) 0 or 1

8. Adequate organ function as determine by the following criteria:
- Absolute neutrophil count (ANC) >=1.5 x 10 000 000 000/L.
- Platelet count >=100 x 10 000 000 000/L
- Calculated creatinine clearance >= 50 mL/min or measured creatinine clearance >=60 mL/min
- AST (SGOT) and ALT (SGPT) =<3 x ULN (AST and ALT =<5 x ULN is acceptable, in the presence of liver metastatses)

- Total bilirubin =<1.5 x ULN

9. Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within the 72 hours prior to starting treatment. Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.

10. Written, voluntary informed consent provided

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:
1. Any histological/cytological evidence of small cell or carcinoid lung cancer.

2. Known central nervous system (CNS) metastasis.
CNS imaging is not required at baseline for patients who have no symptoms suggestive of CNS metastases

3. Any acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or study drug administration or could interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into the study. This includes:
- Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus, erythematosis, rheumatoid arthritis, multiple sclerosis, Sjogren’s syndrome, autoimmune thrombocytopenia, or glomerulonephritis.
- History of allogeneic transplant
- Untreated or uncontrolled superior vena cava syndrome
- Untreated or uncontrolled hypercalcemia
- Requirement for chronic treatment with therapeutic doses of systemic corticosteroids. Use of steroid inhalers, or oral “physiologic replacement” doses of corticosteroids is permitted. Physiological replacement doses will be defined as =<37.5 mg/day of cortisone, =<7.5 mg/day of prednisolone or =<1.0 mg/day of dexamethasone. Patients on other replacement regimens must be discussed with the sponsor.
- Uncontrolled hypertension, unstable angina, myocardial infarction or symptomatic congestive heart failure within the past 12 months or serious uncontrolled cardiac arrhythmia.
- Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HBC) and human immunodeficiency virus (HIV). Serological testing will not be required at baseline for patients who have no symptoms suggestive of infection.
- Pre-existing peripheral neuropathy >= CTC Grade 2.
- Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol.

4. History of any active malignancy (other than NSCLC) during the last 3 years except non melanoma skin cancer, in situ cervical cancer, or cured, early prostate cancer in a patient with PSA level < ULN.

5. Known or suspected hypersensitivity to any of the study drugs (gemcitabin, cisplatin or PF-3512676), study drug classes (pyrimidine analogs, platinum, oligodeoxynucleotide ODN) or excipients in the formulation of study drugs.

6. Female patients who are pregnant or nursing.

7. Inability or lack of willingness to comply with scheduled visits, therapy plans or laboratory tests.

8. Current enrollment in another therapeutic clinical trial.

9. Use of any investigational agent in the past 4 weeks.


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

Health Condition(s) or Problem(s) studied

First line treatment of chemotherapy-naive patients with locally advanced (Stage IIIB with pleural effusion) or metastatic (Stage IV) Non Small Cell Lung Cancer (NSCLC)

Intervention(s)

Product Name: PF-3512676
Product Code: PF-3512676
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not yet available
Current Sponsor code: PF-3512676
Other descriptive name: CPG 7909
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 15-

Trade Name: Gemzar 200 mg Powder for Solution for Infusion; Gemzar 1 g Powder for Solution for Infusion
Product Name: gemcitabine
Product Code: gemcitabine
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: gemcitabine
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1250-

Trade Name: Ciplatin Injection 1 mg/ml
Product Name: cisplatin
Product Code: cisplatin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: cisplatin
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 75-

Primary Outcome(s)

Secondary Objective: - To compare additional measures of efficacy, safety and health-related quality of life and disease/treatment-related symptoms in patients randomized to gemcitabine/cisplatin + PF-3512676 versus patients randomized to gemcitabine/cisplatin alone

- To evaluate the effect of PF-3512676 on the pharmacokinetics of gemcitabine and cisplatin

- To evaluate the pharmacokinetics of PF-3512676 when administered in combination with gemcitabine and cisplatin

Main Objective: - To compare overall survival (OS) in patients randomized to gemcitabine/cisplatin + PF-3512676 (Investigational Treatment Arm) versus that in patients randomized to gemcitabine/cisplatin alone (Control Treatment Arm)

Primary end point(s): Primary Endpoint:

- Overall survival defined as the time from randomization to the date of death due to any cause.

Secondary Endpoints:

- Overall confirmed objective response rate (ORR), defined as the proportion of patients with a confirmed best response characterized as either a complete response (CR) or partial response (PR) (target lesions and tumor response defined according to RECIST guidelines). Confirmed responses are those that persist on a follow-up imaging assessment >=4 weeks after the initial objective documentation of response.

- Duration of response (DR) defined as the time from first documentation of response to the date of progression.

- Progression Free Survival (PFS) defined as the time from randomization to the date of progression or death due any cause, whichever occurs first.

- Time to tumor progression (TTP) defined as the time from randomization to the date of progression.

- Overall safety profile characterized by type, frequency, severity (as graded using NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE), v3.0 and relationship to study therapy of adverse events and laboratory abnormalities.

- Patient Reported Outcome (PRO) changes in scores for health-related quality of life and disease/treatment-related symptoms according to EORTC QLQ-C30 and QLQ-LC-13

- Pharmacokinetic parameters to include but not necessarily limited to Cmax and AUC for gemcitabine, cisplatin, and PF-3512676.

Secondary ID(s)

A8501002