A Study of Paclitaxel/Carboplatin With or Without CDP791 in Patients With Lung Cancer

Study Overview
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Brief Summary
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A 2-part study to examine safety, tolerability and pharmacokinetics (part 1), and anti-tumour effects (part 2), of CDP791 combined with carboplatin and paclitaxel.

Detailed Description
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This is a two part study to investigate the safety and anti-tumour effects of standard chemotherapy, plus an investigational drug (CDP791), in patients with advanced non small cell lung cancer. In part one, patients receive carboplatin and paclitaxel chemotherapy together with one of 2 doses of CDP791. The main aim of this part is to investigate safety and tolerability of carboplatin/paclitaxel plus CDP791. If part one confirms that the combination of drugs is safe and well tolerated, 156 patients will enter part 2. They will be randomized to receive either carboplatin/paclitaxel (C/P) alone, or C/P plus one of 2 doses of CDP791. The main aim of this part of the study is to compare the anti-tumor effects of CDP791 plus C/T with those of C/T alone. Participants will receive up to six cycles of chemotherapy with or without CDP791. Those whose disease stabilizes, or responds, will be eligible to continue to receive CDP791. Participants in the C/T alone arm whose disease progresses will be eligible to receive CDP791 monotherapy. Participants will be followed up longterm, so that survival can be measured.

Official Title
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A Two-Part, Open Label Phase II Trial: Part One, Dose Escalation Safety; Part Two, Randomized/Comparing CDP791 Plus Carboplatin/Paclitaxel With Carboplatin/Paclitaxel Alone in Subjects With Locally Advanced or Metastatic Non-Squamous Non-Small-Cell Lung Cancer

Conditions
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Carcinoma, Non-Squamous Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: CDP791 10mg/kg
* Drug: CDP791 20mg/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria: Male and female subjects with Stage IIIb (with malignant pleural effusion or if no pleural effusion is present subjects who are not candidates for combined modality therapy), Stage IV, or recurrent non-squamous, non-small-cell lung carcinoma. The subject must be aged 18 years or above. The subject must have ECOG performance status of 0 or 1 and a life expectancy of at least three months. Subjects will have measurable disease. The subject must be able to understand the information provided to them and to give written informed consent. Female subjects must be either postmenopausal, surgically sterilized, or using a method of contraception judged reliable by the Investigator. Male subjects must be using a method of contraception judged reliable by the Investigator. Exclusion Criteria: Subjects with squamous cell lung carcinoma. Subjects with lung lesions located centrally in the chest that involve major blood vessels. Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous malignancies are eligible provided that they have been disease free for five years or more. Presence of additional major chronic disease such as hepatic or renal dysfunction, cardiac dysfunction, peripheral vascular disease, evidence of a myocardial infarction within six months of Screening visit, tuberculosis or epilepsy. Subjects known to be infected with hepatitis B or C virus or HIV 1 or 2. Any evidence of serious active infection (ie requiring an iv antibiotic or antiviral agent). Exclusion Criteria:

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carboplatin/Paclitaxel<br>Carboplatin and paclitaxel alone. | Drug: Carboplatin<br>* 10mg/mL vial AUC6. Dosed intravenously over 15-30 minutes immediately following paclitaxel, Day 0 of each cycle. Each cycle to be repeated every three weeks for a maximum of six cycles.<br>* Other names: CBDCA, Paraplatin, JM-8, NSC 241240;Drug: Paclitaxel<br>* 6mg/mL vial 200 mg/m2 iv over three hours, Day 0. Each cycle to be repeated every 3 weeks for a maximum of 6 cycles.<br>* Other names: Taxol, NSC #673089;|
| Experimental: Carboplatin/Paclitaxel/CDP791 10mg<br>Carboplatin and paclitaxel plus CDP791 10mg/kg | Drug: Carboplatin<br>* 10mg/mL vial AUC6. Dosed intravenously over 15-30 minutes immediately following paclitaxel, Day 0 of each cycle. Each cycle to be repeated every three weeks for a maximum of six cycles.<br>* Other names: CBDCA, Paraplatin, JM-8, NSC 241240;Drug: Paclitaxel<br>* 6mg/mL vial 200 mg/m2 iv over three hours, Day 0. Each cycle to be repeated every 3 weeks for a maximum of 6 cycles.<br>* Other names: Taxol, NSC #673089;Drug: CDP791 10mg/kg<br>* CDP791 20mg/mL vial CDP791 diluted (10mg/kg or 20mg/kg) in 0.9% saline will be given as a 200mL iv infusion over approximately 60 minutes following administration of standard chemotherapy.<br>Drug: CDP791 20mg/kg<br>* CDP791 20mg/kg CDP791 diluted (10mg/kg or 20mg/kg) in 0.9% saline will be given as a 200mL iv infusion over approximately 60 minutes following administration of standard chemotherapy.<br>|
| Experimental: Carboplatin/Paclitaxel/CDP791 20mg<br>Carboplatin and paclitaxel plus CDP791 20mg/kg | Drug: Carboplatin<br>* 10mg/mL vial AUC6. Dosed intravenously over 15-30 minutes immediately following paclitaxel, Day 0 of each cycle. Each cycle to be repeated every three weeks for a maximum of six cycles.<br>* Other names: CBDCA, Paraplatin, JM-8, NSC 241240;Drug: Paclitaxel<br>* 6mg/mL vial 200 mg/m2 iv over three hours, Day 0. Each cycle to be repeated every 3 weeks for a maximum of 6 cycles.<br>* Other names: Taxol, NSC #673089;Drug: CDP791 10mg/kg<br>* CDP791 20mg/mL vial CDP791 diluted (10mg/kg or 20mg/kg) in 0.9% saline will be given as a 200mL iv infusion over approximately 60 minutes following administration of standard chemotherapy.<br>Drug: CDP791 20mg/kg<br>* CDP791 20mg/kg CDP791 diluted (10mg/kg or 20mg/kg) in 0.9% saline will be given as a 200mL iv infusion over approximately 60 minutes following administration of standard chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Rate (RR) | Participants are evaluated for response using Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse P et al; 2000). The tumor response rate is calculated as the total number of subjects whose best overall response is a complete response (CR)= disappearance of all target lesions; or a partial response (PR) = >=30 % decrease in the sum of the longest diameter of target lesions, divided by the number of randomized subjects (RS): (CR + PR) / RS. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression free survival (PFS) is defined as time from date of randomization until the date progressive disease (PD) is first recorded or until death, whichever is first. | Up to 57 weeks | 
| Time to Treatment Failure | Time to treatment failure (TTF) is defined as the time from date of randomization until the date of progression, death or, for subjects who discontinued treatment for toxicity reason, their last dosing date, whichever occurs first. | Up to 57 weeks | 
| Overall Survival | Overall survival is defined as the time from date of randomization until the date of death. | Up to 57 weeks | 
| Duration of Overall Response | The duration of overall response is measured from the time measurement criteria are first met for complete response (CR) or partial response (PR), whichever is recorded first, until the first date of documented progressive disease or death. | Up to 57 weeks | 
| Time to Response | Time to response is defined as the time from the first dose of study therapy until measurement criteria are first met for complete response or partial response (whichever is recorded first). | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small-cell-lung cancer, carboplatin, paclitaxel, VEGF, monoclonal antibody