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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00961415
First received: August 18, 2009
Last updated: January 24, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Non-Squamous Non-Small Cell Lung Cancer
Drug: bevacizumab [Avastin]
Drug: cisplatin
Drug: pemetrexed
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression Free Survival During Maintenance Treatment Phase [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival During Maintenance Treatment Phase [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
    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.

  • Best Overall Response Rate During Maintenance Treatment Phase [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Response During Maintenance Treatment Phase [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Disease Control During Maintenance Treatment Phase [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
    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.

  • Incidence of Adverse Events and Serious Adverse Event [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Marked Laboratory Abnormalities [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
    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 ).

  • Quality of Life [ Time Frame: Up to 21 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 376
Study Start Date: August 2009
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 Drug: bevacizumab [Avastin]
7.5mg/kg iv on day 1 of each 3-week cycle
Drug: cisplatin
75mg/m2 iv on day 1 of each 3-week cycle
Drug: pemetrexed
500mg/m2 iv on day 1 of each 3-week cycle
Experimental: Part 2A Drug: bevacizumab [Avastin]
7.5mg/kg iv on day 1 of each 3-week cycle
Active Comparator: Part 2B Drug: bevacizumab [Avastin]
7.5mg/kg iv on day 1 of each 3-week cycle
Drug: pemetrexed
500mg/m2 iv on day 1 of each 3-week cycle

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00961415

  Show 91 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00961415     History of Changes
Other Study ID Numbers: MO22089  2008-007008-27 
Study First Received: August 18, 2009
Results First Received: November 30, 2015
Last Updated: January 24, 2016
Health Authority: Russia: Ministry of Health of the Russian Federation

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
Bevacizumab
Pemetrexed
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 27, 2016