Bevacizumab, Pemetrexed Disodium, and Cisplatin or Erlotinib Hydrochloride and Bevacizumab in Treating Patients With Stage IV Non-Small Cell Lung Cancer. A Multicenter Phase II Trial Including Biopsy at Progression (BIO-PRO Trial).

NCT01116219 | Completed Phase 2

• 3 other identifiers: SAKK 19/09SWS-SAKK-19-09EU-21026
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 22

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether bevacizumab given together with pemetrexed disodium and cisplatin is more effective than erlotinib hydrochloride given together with bevacizumab in treating patients with non-small cell lung cancer. PURPOSE: This phase II trial is studying giving bevacizumab together with pemetrexed disodium and cisplatin to see how well it works compared with giving erlotinib hydrochloride together with bevacizumab in treating patients with stage IV non-small cell lung cancer.

Conditions

Lung Cancer

Keywords

adenocarcinoma of the lung; bronchoalveolar cell lung cancer; large cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 6 months in stratum wtEGFR cohort 1

  at 6 months

Secondary Outcomes (5)

• Progression-free survival

  at 6 months

• Overall survival

  from registration until death

• Best response (RECIST 1.1)

  up to disease progression or start of new treatment

• Adverse events (CTCAE v4.0)

• Molecular markers in tumor tissue and blood

Study Arms (2)

Stratum mut EGFR

ACTIVE COMPARATOR

* Bevacizumab 7.5 mg/kg i.v. every 3 weeks and * Erlotinib 150 mg p.o. daily until progression.

Biological: bevacizumab, erlotinib

Stratum wtEGFR

ACTIVE COMPARATOR

Cohort 1: Induction chemotherapy with * Bevacizumab 7.5 mg/kg i.v. and * Pemetrexed 500 mg/m2 i.v. and * Cisplatin\* 75 mg/m2 i.v. every 3 weeks for a maximum of 4 cycles or until progression. Followed by maintenance therapy in patients without disease progression with * Bevacizumab 7.5 mg/kg i.v. and * Pemetrexed 500 mg/m2 i.v. every 3 weeks until progression. Cohort 2: Induction chemotherapy with * Pemetrexed 500 mg/m2 i.v. and * Cisplatin\* 75 mg/m2 i.v. every 3 weeks for a maximum of 4 cycles or until progression. Followed by maintenance therapy in patients without disease progression with o Pemetrexed 500 mg/m2 i.v. every 3 weeks until progression.

Drug: bevacizumab, pemetrexed, cisplatin

Interventions

bevacizumab, erlotinib BIOLOGICAL

* Bevacizumab 7.5 mg/kg i.v. every 3 weeks and * Erlotinib 150 mg p.o. daily until progression.

Also known as: bevacizumab (Avastin), erlotinib (Tarceva)

Stratum mut EGFR

bevacizumab, pemetrexed, cisplatin DRUG

Induction chemotherapy with * Bevacizumab 7.5 mg/kg i.v. and * Pemetrexed 500 mg/m2 i.v. and * Cisplatin\* 75 mg/m2 i.v. every 3 weeks for a maximum of 4 cycles or until progression. Followed by maintenance therapy in patients without disease progression with * Bevacizumab 7.5 mg/kg i.v. and * Pemetrexed 500 mg/m2 i.v. every 3 weeks until progression.

Also known as: Bevacizumab (Avastin), pemetrexed (Alimta)

Stratum wtEGFR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Before registration, patient must give written informed consent for participation in the trial including tumor biopsy at progression.
• Patient must have the capability to understand informed consent and information given by the investigator on the trial.
• Non-small cell lung cancer (NSCLC), predominant non-squamous subtype (adenocarcinoma, bronchioloalveolar carcinoma, and large cell carcinoma) confirmed by the central pathologist in Basel.
• NSCLC stage IV according to the 7th edition of the TNM classification, including M1a (separate tumor nodule in a contralateral lobe, tumor with pleural nodules or malignant pleural or pericardial effusion) and/or M1b (distant metastasis).
• Most recent diagnostic biopsy paraffin-embedded or only formalin-fixed and sufficient for further molecular analysis as determined by central pathologist in Basel.
• EGFR mutation status determined by local or central pathologist in Basel.
• EDTA blood samples (2 x 5 mL) for translational research projects will be taken before treatment start.
• WHO performance status 0-1 (see Appendix 4).
• Age ≥ 18 years and legally competent person.
• Measurable disease, defined as at least one lesion (outside of irradiated areas) that can be measured in at least one dimension as ≥ 10 mm (≥ 15 mm in case of lymph nodes)according to RECIST v1.1
• Adequate hematological values: Hemoglobin ≥ 100 g/L, neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
• Adequate hepatic function: Bilirubin ≤ 1.5 x ULN, ALT and AP ≤ 3 x ULN (≤ 5 x ULN in case of liver metastases)
• Adequate renal function: Calculated creatinine clearance ≥ 60 mL/min (according to the formula of Cockroft-Gault)
• Urine dipstick for proteinuria \< 2+
• Patient compliance and geographic proximity allow proper staging and follow-up.

You may not qualify if:

• Diagnosis of SCLC, predominantly squamous NSCLC (\>50% by central pathology review) or combined SCLC-NSCLC.
• Patients with intrathoracic tumors invading or abutting major blood vessels.
• Prior chemotherapy or molecular targeted therapy for metastatic disease, with the exception of neoadjuvant or adjuvant chemotherapy if terminated 6 months before registration. Prior radiotherapy to lesion(s) selected for measurement.
• CNS metastases by mandatory CT-scan (MRI is acceptable).
• Anticoagulation, with the exception of low dose heparin or aspirin (≤ 325 mg p.o. daily).
• Active bleeding, including hemoptysis ≥ grade 2 (defined as bright red blood of at least 5 mL per episode within the last 4 weeks of registration). Minor hemoptysis is allowed.
• Yellow fever vaccination within the 30 days prior to registration.
• Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
• Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, or interfering with compliance for oral drug intake.
• Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry.
• Evidence of other medical condition which would impair the ability of the patient to participate in the trial or might preclude therapy with trial drugs (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, active infection, uncontrolled diabetes mellitus; uncontrolled arterial hypertension ≥ 150/100 mmHg, history of myocardial infarction in the last 3 months, history of hemorrhagic disorders, non healing wound, ulcer or bone fracture)
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to registration
• Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
• Any concomitant drugs contraindicated for use with the trial drugs according to the Swissmedic-approved product information.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (22)

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Saint Claraspital AG

Basel, CH-4016, Switzerland

Location

Clinical Cancer Research Center at University Hospital Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, CH-6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Kantonsspital Freiburg

Fribourg, 1700, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Pluridisciplinaire d' Oncologie

Lausanne, 1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Kantonsspital Luzern

Luzerne, CH-6000, Switzerland

Location

Kantonsspital Olten

Olten, 4600, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Spital Uster

Uster, 8610, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8401, Switzerland

Location

Onkozentrum Hirslanden

Zurich, 8008, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8044, Switzerland

Location

City Hospital Triemli

Zurich, CH-8063, Switzerland

Location

Related Publications (1)

• Gautschi O, Rothschild SI, Li Q, Matter-Walstra K, Zippelius A, Betticher DC, Fruh M, Stahel RA, Cathomas R, Rauch D, Pless M, Peters S, Froesch P, Zander T, Schneider M, Biaggi C, Mach N, Ochsenbein AF; Swiss Group for Clinical Cancer Research. Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Maintenance Therapy for Patients With Advanced Nonsquamous Non-Small-cell Lung Cancer: Update From the Swiss Group for Clinical Cancer Research (SAKK) 19/09 Trial. Clin Lung Cancer. 2017 May;18(3):303-309. doi: 10.1016/j.cllc.2016.11.007. Epub 2016 Nov 23.

  PMID: 27993482 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar; Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; Erlotinib Hydrochloride; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Oliver Gautschi, MD

  Luzerner Kantonsspital

  STUDY CHAIR

• Adrian Ochsenbein, MD

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

• Nicolas Mach, MD

  Hopital Cantonal Universitaire de Geneve HUG

  PRINCIPAL INVESTIGATOR

• Sacha Rothschild, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2010
• First Posted: May 4, 2010
• Study Start: June 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: May 1, 2016
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (22)