AVAPERL1 Study: A Study of Avastin (Bevacizumab) With or Without Pemetrexed as Maintenance Therapy After Avastin in First Line in Patients With Non-Squamous Non-Small Cell Lung Cancer

Non-Squamous Non-Small Cell Lung Cancer Clinical Trial

Official title:

Open-label Study of Bevacizumab Maintenance Therapy (AVASTIN®) With or Without Pemetrexed After First-line Chemotherapy With Bevacizumab-cisplatin-pemetrexed in Patients With Advanced, Metastatic or Recurrent Non-squamous Non-small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00961415
• Other study ID #: MO22089
• Secondary ID: 2008-007008-27
• Status: Completed
• Phase: Phase 3
• First received: August 18, 2009
• Last updated: January 24, 2016
• Start date: August 2009
• Est. completion date: May 2011

Study information

• Verified date: January 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

This open-label study will assess the efficacy and safety of Avastin with or without pemetrexed as maintenance therapy in patients with advanced, metastatic or recurrent non-small cell lung cancer. In Part 1, patients will receive 4 cycles of treatment with Avastin (7.5mg/kg iv) plus cisplatin (75mg/m2 iv) plus pemetrexed (500mg/m2 iv) on day 1 of each 3-week cycle. In Part 2, patients responding to treatment will be randomized to receive further treatment cycles of Avastin (7.5mg/kg iv every 3 weeks) with or without pemetrexed (500mg/m2 iv every 3 weeks). Anticipated time on study treatment is until disease progression. Target sample size is <500 individuals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 376
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adults >/=18 years of age

• inoperable, locally advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC)

• at least 1 measurable lesion meeting RECIST criteria

• ECOG performance status 0-2

• adequate hematological, liver and renal function

Exclusion Criteria:

• prior chemotherapy or treatment with another systemic anti-cancer agent

• malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer or DCIS

• evidence of tumor invading major blood vessels

• current or recent use of aspirin (>325mg/day) or full-dose anticoagulants or thrombolytic agents for therapeutic purposes

• history of haemoptysis >/=grade 2

• clinically significant cardiovascular disease

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Squamous Non-Small Cell Lung Cancer

Intervention

Drug:
• bevacizumab [Avastin]
7.5mg/kg iv on day 1 of each 3-week cycle
• cisplatin
75mg/m2 iv on day 1 of each 3-week cycle
• pemetrexed
500mg/m2 iv on day 1 of each 3-week cycle

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

France,  Germany,  Greece,  Italy,  Korea, Republic of,  Netherlands,  Russian Federation,  Spain,  Sweden,  Switzerland,  Turkey,  United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival During Maintenance Treatment Phase	Progression free survival (PFS) is defined as the time from randomization to the date of documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) , or the date of occurrence of a second primary cancer, or date of death from any cause, whichever comes first. Progression is defined using (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions.Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.	Up to 21 months	No
Secondary	Overall Survival During Maintenance Treatment Phase	Overall survival (OS) is assessed from the date of first induction treatment until the date of death. Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.	Up to 21 months	No
Secondary	Best Overall Response Rate During Maintenance Treatment Phase	The best overall response rate (BORR) is defined as the percentage of participants having achieved confirmed Complete Response (CR) and Partial Response (PR) as the best overall response. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a greater than or equal to (=) 30% decrease under baseline of the sum of diameters of all target lesions. Stable disease (SD) is defined as steady state of disease with neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.	Up to 21 months	No
Secondary	Duration of Response During Maintenance Treatment Phase	Duration of response is defined as the time in months from the initial start of response PR or better to the earlier of documented PD or death due to any cause. Participants who had neither progressed nor died at the date of clinical cutoff, who withdrew from the study, were lost to follow-up, or were without documented disease progression were censored at the date of the last available tumor assessment. The analysis was based on all participants with measurable disease at baseline who achieved response.Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.	Up to 21 months	No
Secondary	Duration of Disease Control During Maintenance Treatment Phase	Duration of disease control is defined as the time in months from randomization to the earlier of documented PD or death due to any cause. Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.	Up to 21 months	No
Secondary	Incidence of Adverse Events and Serious Adverse Event	An adverse events (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An serious adverse event (SAE) is any experience that suggests a significant hazard, contraindication, side effect, or precaution.	Up to 21 months	No
Secondary	Number of Participants With Marked Laboratory Abnormalities	Marked laboratory abnormalities were defined as those values that were outside the reference range and showed a clinically relevant change from Baseline. The reference range for Platelets was 100-550 (10^9/L), for White blood cells (WBC) was 3.0-18.0 (10^9/L), for Lymphocytes was 0.70-7.60 (10^9/L), and Neutrophil 1.50-9.25 (10^9/L ).	Up to 21 months	No
Secondary	Quality of Life	European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Cancer 30 (EORTC QLQ-C30): included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Lung Cancer 13 [EORTC QLQ-LC13]consisted of 1 multi-item scale and 9 single items that assessed the specific symptoms (dyspnea, cough, hemoptysis, and site specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of lung cancer participants receiving chemotherapy. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity. QOL was assessed using Pre-Induction Baseline (Pre-ind BL), Maintenance (MTC), End of study (EOS) cycles.	Up to 21 months	No