TS Stratified Chemotherapy and VEGF Inhibition in Non-Squamous Non-Small Cell Lung Cancer - Stage IV

NCT01674738 | Withdrawn Phase 2 DMC

• 2 other identifiers: ABC-2011-NSCLC-032011-002145-35
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study wants to determine the activity of a first-line treatment related to Thymidylate Synthetase (TS) Expression. Patients with the diagnosis of non-squamous advanced Non-Small-Cell Lung-Cancer (Stage IV) and without evidence of EGFR mutation may be enclosed in this clinical trial.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non Small Cell Lung Cancer; NSCLC Stage IV; Non-Squamous Advanced Non-Small-Cell Lung-Cancer (Stage IV)

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Recruitment period 1,5 years, observation period 2 years

Secondary Outcomes (4)

• Overall survival

  Recruitment period 1,5 years, observation period 2 years

• Quality of life

  Screening, day 1, end of cycle 1, end of treatment (for each patient)

• Response rate

  Screening, prior to cycle 3, end of cycle 4, evry 6 weeks after end of cycle 4, end of treatment (for each patient)

• Molecular investigations

  Day 1, prior to cycle 3, end of cycle 4, end of treatment

Study Arms (2)

Pemetrexed, Cisplatin, Bevacizumab

EXPERIMENTAL

Stratum A

Drug: Pemetrexed; Drug: Cisplatin; Drug: Bevacizumab

Pemetrexed, Cisplatin, Bevazizumab

EXPERIMENTAL

Stratum B:

Drug: Pemetrexed; Drug: Cisplatin; Drug: Bevacizumab

Interventions

Pemetrexed DRUG

500 mg/m2 i.v. on day 1 (three-week cycle)

Pemetrexed, Cisplatin, Bevacizumab; Pemetrexed, Cisplatin, Bevazizumab

Cisplatin DRUG

75 mg/m2 i.v. on day 1 (three-week cycle)

Pemetrexed, Cisplatin, Bevacizumab; Pemetrexed, Cisplatin, Bevazizumab

Bevacizumab DRUG

7,5 mg/kg i.v. on day 1 (three-week cycle)

Pemetrexed, Cisplatin, Bevacizumab; Pemetrexed, Cisplatin, Bevazizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmed Non-Small-Cell lung cancer
• Tumor stage IV (UICC 7th Version)
• The following histological tumor types are eligible:
• Adenocarcinoma (including adenocarcinomas with bronchioloalveolar differentiation)
• Large Cell carcinoma without neuroendocrine differentiation
• Mixed Cell Carcinoma without small cell fraction and without predominant squamous cell fraction
• undifferentiated non-small-cell-carcinoma
• No previous chemotherapy for stage IV NSCLC
• Adjuvant or neoadjuvant chemotherapy for NSCLC must be completed at least one year prior to study enrolment (from end of chemotherapy)
• No previous treatment with Pemetrexed or Bevacizumab
• Patients with prior radiation therapy may be eligible for this study if they meet the following guidelines:
• Previous radiation therapy is allowed to \<25% of the bone marrow (Cristy and Eckerman 1987), but should have been limited and must not have included whole pelvis radiation.
• Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia).
• Prior thoracic radiotherapy must be completed 30 days before study enrollment.
• Lesions that have been radiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.

You may not qualify if:

• Histological confirmed predominant squamous cell carcinoma
• Presence of activating EGFR mutations in exons 18-21
• Pregnancy or lactation period
• Have known central nervous system (CNS) disease, other than stable, treated brain metastasis. Stable, treated brain metastasis is defined as metastasis having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and post-treatment brain imaging (CT scan or magnetic resonance imaging \[MRI\]). Patients should be off corticosteroids for 1 week (7 days) at the time of the post-treatment brain CT/MRI. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy, (stereotactic) radiosurgery (Gamma Knife, linear particle accelerator, or equivalent), or a combination as deemed appropriate by the treating physician, and must have been completed \> 8 days prior to Day 1 of Cycle 1. Patients with signs of a fresh bleeding into one or more cerebral metastases or with CNS metastases treated by neurosurgical resection or brain biopsy performed within 8 weeks prior to Day 1 of Cycle 1 will be excluded.
• Evidence of tumor invading or abutting major blood vessels
• Presence of a tracheobronchial fistula
• History of abdominal fistula or fistulisation of urogenital tract, gastrointestinal perforation or intra-abdominal abscess, inflammatory bowel disease, or diverticulitis within 6 months prior to study start
• Treatment with an investigational new drug, currently or within the last 28 days, and/or participation in another clinical trial, currently or during the last 12 weeks, and/or previous participation in this study.
• History or presence of a mental disease or condition such as to interfere with the patient's ability to understand the requirements of the study and the intake of study medication according to study protocol.
• Patients with any clinically significant disease that in the opinion of the investigator is likely to put the patient at risk or to interfere with the evaluation of the patient's safety and of the study outcome. This includes, but is not limited to:
• Immediate need for therapeutic intervention (e.g.: upper inflow congestion or poststenotic pneumonia).
• Clinically significant cardiac disease (e.g. right-sided heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.
• Have a history of hypertension, unless hypertension is well controlled upon study entry (\<150/90 mm Hg) and the patient is on a stable regimen of antihypertensive therapy. Patients should not have any prior history of hypertensive crisis or hypertensive encephalopathy.
• Non healing wound, ulcer or bone fracture
• Fresh thrombosis (within the last two weeks) under full dose therapy with anticoagulants.

Sponsors & Collaborators

• Aktion Bronchialkarzinom e.V.: lead
• Roche Pharma AG: collaborator
• Eli Lilly and Company: collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Cisplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gunther Wiest, MD

  Asklepios Klinik Harburg, D-21075 Hamburg, Germany

  PRINCIPAL INVESTIGATOR

• Prof. Dr. Martin Wolf, MD

  Klinikum Kassel GmbH, D-34125 Kassel

  STUDY CHAIR

• Dr. Monika Serke, MD

  Lungenklinik Hemer, D-58675 Hemer, Germany

  STUDY CHAIR

• Prof. Dr. Michael Thomas, MD

  Thoraxklinik Heidelberg, D-69126 Heidelberg, Germany

  STUDY CHAIR

• Rudolf M. Huber, MD

  Klinikum der Universität München, D-80336 München, Germany

  STUDY CHAIR

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: August 23, 2012
• First Posted: August 29, 2012
• Last Updated: October 11, 2013

Record last verified: 2013-10