Paclitaxel, Carboplatin, and Dimethylxanthenone Acetic Acid in Treating Patients With Extensive-Stage Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT01057342
First received: January 26, 2010
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Dimethylxanthenone acetic acid may stop the growth of small cell lung cancer by blocking blood flow to the tumor. Giving paclitaxel and carboplatin together with dimethylxanthenone acetic acid may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving paclitaxel and carboplatin together with dimethylxanthenone acetic acid and to see how well they work in treating patients with extensive-stage small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Drug: carboplatin
Drug: paclitaxel
Drug: vadimezan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Carboplatin and Paclitaxel Plus ASA404 as First Line Chemotherapy for Extensive-Stage Small-Cell Lung Cancer (ES-SCLC): A Phase II Trial

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Progression-free survival rate [ Time Frame: at 24 weeks (6 months) ] [ Designated as safety issue: No ]

    The status of progression free survival at 24 weeks (+/- 2 weeks) from trial registration will be assessed. A PFS event is defined as (whichever occurs first):

    • Relapse or progression assessed according to the RECIST 1.1 criteria (Appendix 1)
    • Death of any cause.


Secondary Outcome Measures:
  • Adverse events by NCI CTCAE v3.0 [ Time Frame: until 30 days after trial therapy end ] [ Designated as safety issue: Yes ]
  • Best objective response OR complete or partial response according to RECIST 1.1 [ Time Frame: whilst receiving the trial therapy ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Defined as the time from registration until documented Small-cell Lung Cancer (SCLC) progression or death as a result of SCLC. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Time from registration until death as a result of any cause. ] [ Designated as safety issue: No ]
  • One-year survival rate [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
    Patients alive one year after trial registration


Enrollment: 17
Study Start Date: January 2010
Study Completion Date: July 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel, Carboplatin, ASA404 Drug: carboplatin
AUC 6 i.v. given after paclitaxel as the second treatment on day 1 of each 3-week cycle.
Other Name: Paraplatin
Drug: paclitaxel
175 mg/m2 i.v. first treatment on day 1 of each 3-week cycle.
Other Name: Abraxane Taxol
Drug: vadimezan
1800 mg/m2 i.v. following the administration of paclitaxel and carboplatin on day 1 of each 3-week cycle
Other Name: ASA404

Detailed Description:

OBJECTIVES:

Primary

  • To assess the 24-week (6 months) progression-free survival of patients with extensive stage small cell lung cancer treated with paclitaxel, carboplatin, and dimethylxanthenone acetic acid.

Secondary

  • To assess efficacy and safety of this regimen in these patients.
  • To evaluate predictive molecular markers for gene expression analyses, serum proteomics, and pharmacogenomics. (exploratory)

OUTLINE: This is a multicenter study.

Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and dimethylxanthenone acetic acid IV over 20 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples may be collected periodically for predictive molecular markers for gene expression analysis, plasma proteomics, and pharmacogenomics.

After completion of study treatment, patients are followed every 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically (preferred) or cytologically confirmed small-cell lung carcinoma (SCLC) by surgical biopsy, brushing, washing, OR core needle aspiration (sputum cytology alone not acceptable)

    • Extensive stage or stage IV disease, including patients with malignant pleural or pericardial effusion

      • No pleural effusion that causes ≥ CTC grade 2 dyspnea
  • Not suitable for potentially curative combined-modality treatment for this disease
  • Measurable or non-measurable disease
  • No CNS metastases

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Hemoglobin ≥ 10.0 g/dL
  • Absolute neutrophils ≥ 2.0 x 10^9/L (without the use of growth factors)
  • Platelet count ≥ 100 x 10^9/L
  • Bilirubin ≤ 1.5 x the upper limit of normal (ULN)
  • ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
  • Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
  • Creatinine clearance ≥ 45 mL/min
  • INR ≤ 1.5
  • Magnesium, potassium, and calcium (corrected for albumin) normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after completion of study therapy
  • No recent hemoptysis associated with SCLC (> 1 teaspoon in a single episode within 4 weeks)
  • No other malignancy within the past 5 years except for nonmelanoma skin cancer or cervical cancer in situ
  • Must not have a history of any of the following conditions:

    • Myocardial infarction within the past 12 months
    • Uncontrolled hypertension (systolic BP > 160 mm Hg and/or diastolic BP > 90 mm Hg) or poor compliance with anti-hypertensive regimen
    • Sustained ventricular tachycardia
    • Ventricular fibrillation or Torsades de Pointes
    • Long QT syndrome
    • QTc of > 450 msec
    • NYHA class III or IV congestive heart failure
    • Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
    • Right bundle branch block and left anterior hemiblock (bifascicular block)
    • Bradycardia (defined as heart rate < 50 beats per minute)
    • Cardiac arrhythmias (i.e., symptomatic, but may not require medications) CTCAE grade ≥ 2
  • No significant neurologic or psychiatric disorder that would compromise study participation
  • No peripheral sensory neuropathy with functional impairment ≥ CTC grade 2 (regardless of cause)
  • No concurrent severe and/or uncontrolled medical disease, including any of the following:

    • Uncontrolled diabetes
    • Chronic renal disease
    • Chronic liver disease
    • Confirmed diagnosis of HIV infection
    • Active uncontrolled infection
  • No serious underlying medical condition, in the judgment of the investigator, that would impair the patient's ability to participate in the trial
  • No known hypersensitivity to study drugs or to any other component of the study drugs (taxanes or other drugs formulated in Cremophor EL [polyoxyethylated castor oil])

PRIOR CONCURRENT THERAPY:

  • Recovered from all prior therapy
  • No prior systemic chemotherapy, immunotherapy, or biologic anti-cancer therapy
  • More than 2 weeks since prior and no concurrent radiotherapy

    • Localized palliative radiotherapy to symptomatic bone metastases allowed
  • More than 2 weeks since minor surgery

    • Insertion of a vascular access device allowed
  • More than 3 weeks since prior dimethylxanthenone acetic acid for prophylactic cranial irradiation
  • More than 4 weeks since major surgery (defined by the use of general anesthesia)
  • At least 30 days since prior and no other concurrent investigational drugs or anti-cancer therapy
  • No treatment in a clinical trial within 30 days prior to trial entry
  • No concurrent therapy with a risk of causing Torsades de Pointes
  • No concurrent drugs that would be contraindicated for use with study drugs
  • No factors with the potential to prolong QT interval
  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: NCT01057342

Locations
Switzerland
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Saint Claraspital AG
Basel, Switzerland, CH-4016
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, Switzerland, CH-6500
Inselspital Bern
Bern, Switzerland, CH-3010
Spitalzentrum Biel
Biel, Switzerland, CH-2501
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Olten
Olten, Switzerland, CH-4600
Onkologie Schaffhausen
Schaffhausen, Switzerland, CH-8200
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Regionalspital
Thun, Switzerland, 3600
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
Klinik Hirslanden
Zurich, Switzerland, CH-8032
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Martin Frueh, MD Cantonal Hospital of St. Gallen
Study Chair: Miklos Pless, MD Kantonsspital Winterthur KSW
Study Chair: Oliver Gautschi, MD University Hospital Inselspital, Berne
  More Information

Additional Information:
Publications:
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01057342     History of Changes
Other Study ID Numbers: SAKK 15/08, SWS-SAKK-15-08, EUDRACT-2009-016960-34, EU-21001, NOVARTIS-CASA404ACCH01T
Study First Received: January 26, 2010
Last Updated: April 9, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
extensive stage small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
5,6-dimethylxanthenoneacetic acid
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 23, 2014