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AzTrials

Lung CancerPhase 2NCT01116219

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).

A Phase 2 study testing bevacizumab, erlotinib and bevacizumab, pemetrexed, cisplatin in people with Lung Cancer, run by Swiss Cancer Institute at 22 sites in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer
What is being tested?
bevacizumab, erlotinib and bevacizumab, pemetrexed, cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
149 participants
Where
22 sitesSwitzerland
Study dates
Jun 2010to May 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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+
  • Women are not breastfeeding. Women with child-bearing potential are using effective contraception (see 9.2.4 and 9.3.5), are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. A negative pregnancy test before inclusion into the trial is required for all women with childbearing potential. Men agree not to father a child during participation in the trial or during the 12 months thereafter.
  • Patient compliance and geographic proximity allow proper staging and follow-up.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

Switzerland22 sites

  • Kantonsspital Aarau

    Aarau, CH-5001

  • Kantonsspital Baden

    Baden, 5404

  • Saint Claraspital AG

    Basel, CH-4016

  • Clinical Cancer Research Center at University Hospital Basel

    Basel, CH-4031

  • Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

    Bellinzona, CH-6500

  • Inselspital Bern

    Bern, CH-3010

  • Spitalzentrum Biel

    Biel, CH-2501

  • Kantonsspital Bruderholz

    Bruderholz, CH-4101

  • Kantonsspital Graubuenden

    Chur, CH-7000

  • Kantonsspital Freiburg

    Fribourg, 1700

  • Hopital Cantonal Universitaire de Geneve

    Geneva, CH-1211

  • Centre Pluridisciplinaire d' Oncologie

    Lausanne, 1011

  • Kantonsspital Liestal

    Liestal, CH-4410

  • Kantonsspital Luzern

    Luzerne, CH-6000

  • Kantonsspital Olten

    Olten, 4600

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

  • Regionalspital

    Thun, 3600

  • Spital Uster

    Uster, 8610

  • Kantonsspital Winterthur

    Winterthur, CH-8401

  • Onkozentrum Hirslanden

    Zurich, 8008

  • UniversitaetsSpital Zuerich

    Zurich, CH-8044

  • City Hospital Triemli

    Zurich, CH-8063

Other trials in Switzerland

About this study

Official title: Bevacizumab, Pemetrexed and Cisplatin, or Erlotinib and Bevacizumab for Advanced Non-Squamous NSCLC Stratified by EGFR Mutation Status. A Multicenter Phase II Trial Including Biopsy at Progression (BIO-PRO Trial).

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.

Read the detailed description

OBJECTIVES:

Primary

  • To demonstrate that tailored therapy, according to tumor histology and EGFR-mutation status, and the introduction of novel drug combinations in the frontline treatment of patients with stage IV non-squamous non-small cell lung cancer, is promising for further investigation.

Secondary

  • To prospectively explore molecular markers of clinical outcomes.

OUTLINE: This is a multicenter study. Patients are stratified according to EGFR(epidermal growth factor receptor)-mutation status (mutated vs wildtype). Patients are assigned to 1 of 2 groups.

  • mutEGFR (mutated epidermal growth factor receptor) group: Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • wtEGFR (wildtype epidermal growth factor receptor) group cohort 1:
  • Induction chemotherapy: Patients receive bevacizumab IV over 30-90 minutes, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Maintenance therapy: Patients without progressive disease receive bevacizumab IV over 30-90 minutes and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression.

Blood and tissue specimens are collected for EGFR and molecular markers analysis, including gene expression, mutation, and pharmacogenomic analyses.

After completion of study treatment, patients are followed every 3 months.

  • wtEGFR (wildtype epidermal growth factor receptor) group cohort 2:
  • Induction chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes, and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Maintenance therapy: Patients without progressive disease receive pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression.

Blood and tissue specimens are collected for EGFR and molecular markers analysis, including gene expression, mutation, and pharmacogenomic analyses.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 129 evaluable patients (77 in cohort 1 and 52 in cohort 2) with wtEGFR status and 20 patients with mutEGFR status will be accrued for this study.

Conditions
Lung Cancer
Being tested
bevacizumab, erlotinib, bevacizumab, pemetrexed, cisplatin
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
Medical subject headings
Lung Neoplasms, Adenocarcinoma of Lung, Adenocarcinoma, Bronchiolo-Alveolar, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bevacizumab, erlotinibBiological

    Also called bevacizumab (Avastin), erlotinib (Tarceva)

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

  • bevacizumab, pemetrexed, cisplatinDrug

    Also called Bevacizumab (Avastin), pemetrexed (Alimta)

    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.
Study groups in NCT01116219
Study groupRoleWhat they receive
Stratum mut EGFRActive comparator* Bevacizumab 7.5 mg/kg i.v. every 3 weeks and * Erlotinib 150 mg p.o. daily until progression.
Receives: Biological: bevacizumab, erlotinib
Stratum wtEGFRActive comparatorCohort 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.
Receives: Drug: bevacizumab, pemetrexed, cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: at 6 months

Secondary outcomes (5)

  1. Progression-free survival

    Measured: at 6 months

  2. Overall survival

    Measured: from registration until death

  3. Best response (RECIST 1.1)

    Measured: up to disease progression or start of new treatment

  4. Adverse events (CTCAE v4.0)

  5. Molecular markers in tumor tissue and blood

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionJul 2014
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
149 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01116219
Sponsor's protocol ID
SAKK 19/09
Other IDs
SWS-SAKK-19-09, EU-21026
Status last verified
May 2019
First submitted
27 Apr 2010
Last updated
15 May 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 27993482

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab, erlotinib and bevacizumab, pemetrexed, cisplatin in people with Lung Cancer, run by Swiss Cancer Institute at 22 sites in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival at 6 months in stratum wtEGFR cohort 1 (time frame: at 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01116219, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2019.

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