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

• ClinicalTrials.gov Identifier: NCT00961415
• Recruitment Status: Completed
• First Posted: August 19, 2009
• Results First Posted: February 22, 2016
• Last Update Posted: February 22, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: August 18, 2009
• First Posted Date: August 19, 2009
• Results First Submitted Date: November 30, 2015
• Results First Posted Date: February 22, 2016
• Last Update Posted Date: February 22, 2016
• Study Start Date: August 2009
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2016)

Progression Free Survival During Maintenance Treatment Phase [ Time Frame: Up to 21 months ]

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.

• Original Primary Outcome Measures (submitted: August 18, 2009): Progression-free survival [ Time Frame: tumour assessment before cycle 3, at 2nd cycle of maintenance therapy and every 9 weeks thereafter ]

Current Secondary Outcome Measures (submitted: January 24, 2016)

• Overall Survival During Maintenance Treatment Phase [ Time Frame: Up to 21 months ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

Original Secondary Outcome Measures (submitted: August 18, 2009)

• Response rate, disease control rate,duration of response, overall survival [ Time Frame: tumour assessment before cycle 3, at 2nd cycle of maintenance therapy and every 9 weeks thereafter ]
• Safety and tolerability: AEs, laboratory parameters [ Time Frame: throughout study, laboratory assessments every 3 weeks ]
• Quality of life [ Time Frame: EORTC-QLQ assessments every 2 cycles ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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)
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Squamous Non-Small Cell Lung Cancer

Intervention

• 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

Study Arms

• Experimental: Part 1
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: cisplatin
  • Drug: pemetrexed
• Experimental: Part 2A
  Intervention: Drug: bevacizumab [Avastin]
• Active Comparator: Part 2B
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: pemetrexed

• Publications *: Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikstrom A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. doi: 10.1200/JCO.2012.42.3749. Epub 2013 Jul 8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 24, 2016): 376
• Original Estimated Enrollment (submitted: August 18, 2009): 362
• Actual Study Completion Date: May 2011
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Greece, Italy, Korea, Republic of, Netherlands, Russian Federation, Spain, Sweden, Switzerland, Turkey, United Arab Emirates
• Removed Location Countries: Kuwait, Portugal

Administrative Information

• NCT Number: NCT00961415
• Other Study ID Numbers: MO22089; 2008-007008-27
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Clinical Trials, Study Director, Hoffmann-La Roche
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: January 2016