Histology-based Consolidation Chemotherapy Following Concurrent Chemo-radiotherapy for Inoperable Stage III Non-small Cell Lung Cancer (NSCLC)

This study is currently recruiting participants.
Verified on August 2011 by Louisiana State University Health Sciences Center Shreveport

First Received on April 12, 2011.  
Last Updated on August 31, 2011  
History of Changes
This Clinical Trial Sponsored By: Syed Jafri
Information provided by (Responsible Party): Syed Jafri, Louisiana State University Health Sciences Center Shreveport
ClinicalTrials.gov Identifier: NCT01336543
 

Purpose for Clinical Trial

This is a pilot phase II study of histology based consolidation chemotherapy in patients with inoperable stage III NSCLC following concurrent chemo-radiotherapy. Patients with inoperable stage III NSCLC would be treated with standard concurrent chemo-radiotherapy and subsequently those with non-squamous histology would be offered 4 cycles of consolidation pemetrexed and those with squamous histology 4 cycles of consolidation with gemcitabine.

Condition Study Intervention Clinical Trial Phase
Stage III Non-small Cell Lung Cancer Drug: Chemotherapy following concurrent Chemoradiotherapy Phase II

Study Type: Study Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Study Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study: Phase II Study of Histology-based Consolidation Chemotherapy Following Concurrent Chemo-radiotherapy for Inoperable Stage III Non-small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics:
Cancer
Lung Cancer
Drug Information available for:
Gemcitabine
Gemcitabine hydrochloride
Pemetrexed
Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by Louisiana State University Health Sciences Center Shreveport:

Primary Outcome Measures For Clinical Trial:

  • Progression free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    From date of registration to date of first observation of progressive disease, death due to any cause or symptomatic deterioration.

Estimated Enrollment: 22
Study Start Date: March 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

Active Treatment: Experimental

  1. NSCLC (Non-Small Cell Lung Cancer)
  2. PE (Cisplatin 50mg/m2 on days 1,8,29,36 Etoposide 80 mg/m2 days 1-3 and 29-31)
  3. Radiation 59.4 Gy with 2 cycles of PE
  4. (Non-squamous histology) Pemetrexed consolidation 500mg/m2 every 21 days for 4 cycles
  5. (Squamous histology) Gemcitabine consolidation 1000mg/m2 days 1,8, every 21 days for 4 cycles
Study Intervention: Drug: Chemotherapy following concurrent Chemoradiotherapy
Drug: Chemotherapy following concurrent Chemoradiotherapy

  1. NSCLC (Non-Small Cell Lung Cancer)
  2. PE (Cisplatin 50mg/m2 on days 1,8,29,36 Etoposide 80mg/m2 days 1-3 and 29-31)
  3. Radiation 59.4 Gy with 2 cycles of PE
  4. (Non-squamous histology) Pemetrexed consolidation 500mg/m2 every 21 days for 4 cycles
  5. (Squamous histology) Gemcitabine consolidation 1000mg/m2 days 1,8, every 21 days for 4 cycles
Other Names:
  • Pemetrexed
  • Gemcitabine

Detailed Description:

Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer related mortality in US (1). About 22% of patients diagnosed with NSCLC have locally advanced or stage III disease at the time of diagnosis (2). 5 years survival for stage III lung cancer is 23% which is much less than survival in similar stage breast and Colon Cancers (2). Current standard of care for inoperable stage III NSCLC is concurrent chemo-radiotherapy as established by a study SWOG 9019 (3). Surgery following concurrent chemo-radiotherapy has been evaluated in a large Phase III clinical trial in patients with Stage III (N2) disease which did not show any improvement in overall survival from surgery as compared to concurrent chemo-radiotherapy alone.(4). These two studies demonstrated that the most common site of cancer relapse in patients with stage III disease was distant metastasis, 65% (3) and 57% (4) respectively.

These observations have led to the idea that perhaps giving additional chemotherapy following definitive concurrent chemo-radiotherapy may prevent distant relapse in stage III NSCLC.

This idea was evaluated in a Phase II study SWOG S9504 in which patients with stage III NSCLC were treated with concurrent chemo-radiotherapy followed by 4 cycles of docetaxel consolidation (5). Four cycles of docetaxel consolidation showed an impressive improvement in median OS to 26 months.

This idea of docetaxel consolidation was subsequently evaluated in a large phase III trial in which patients inoperable stage III NSCLC after receiving concurrent chemo-radiotherapy were randomized to docetaxel consolidation versus observation (6). However, this study showed no improvement in OS between the docetaxel arm and the observation arm. Many patients in docetaxel arm developed pneumonitis and febrile neutropenia.

Histology based selection of chemotherapy is now standard of for stage IV metastatic NSCLC. A large randomized Phase III trial from Europe showed that a combination of Cisplatin and Pemetrexed is more effective in patients with non-squamous histology and a combination of Cisplatin and Gemcitabine showed efficacy in patients with squamous cell histology (7). Recently maintenance Pemetrexed was evaluated in advanced NSCLC and showed improvement in PFS and OS in patients with non-squamous histology (8). Similarly maintenance gemcitabine has also been evaluated in large Phase III clinical trial after initial chemotherapy with Cisplatin and Gemcitabine (9).

Since most patients with inoperable stage III NSCLC develop distant metastasis following definitive concurrent chemo-radiotherapy there clearly is a need to give addition treatment for these patients. Docetaxel consolidation has not been shown to be successful as noted above. Perhaps tailoring chemotherapy according to histology may result in improvement in PFS and OS in these patients.

Based on this hypothesis the investigators intend to do a pilot phase II study of histology based consolidation chemotherapy in patients with inoperable stage III NSCLC following concurrent chemo-radiotherapy. Patients with inoperable stage III NSCLC would be treated with standard concurrent chemo-radiotherapy and subsequently those with non-squamous histology would be offered 4 cycles of consolidation pemetrexed and those with squamous histology 4 cycles of consolidation with gemcitabine.

  Eligibility

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

Inclusion Criteria:

  1. Adult patients 18 years and older with histology proven NSCLC with inoperable stage III A or IIIB disease.
  2. Inoperable stage III

Leave a Reply

You can use these HTML tags

<a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>

  

  

  

three × four =