Dose-Dense Induction/Neoadjuvant Chemotherapy in Locally Advanced Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT02157116
• Recruitment Status: Terminated
• First Posted: June 5, 2014
• Results First Posted: July 4, 2014
• Last Update Posted: July 4, 2014
• Sponsor: Duke University
• Collaborator: Sanofi
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

Dose-dense chemotherapy is a chemotherapy treatment plan in which drugs are given with less time between treatments than in standard chemotherapy. The two chemotherapy drugs used in this study, docetaxel and cisplatin, are approved for the treatment of lung cancer when given every 21 days. This study is exploring the response to chemotherapy when these drugs are given every 14 days. In addition, genetic tests will be performed on pre-treatment specimens to identify signatures that may predict chemotherapy sensitivity or resistance.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: cisplatin; Drug: Docetaxel; Drug: Pegfilgrastim	Phase 2

Detailed Description:

All patients will receive induction chemotherapy with cisplatin and docetaxel. Pegfilgrastim will be administered approximately 24 hours following the end of the day 1 chemotherapy infusion. Cycles will be repeated every 2 weeks for 3 cycles. Patients deemed to be resectable will undergo surgical resection followed by postoperative thoracic radiotherapy. Patients deemed inoperable will additionally receive concurrent chemoradiotherapy. Response, using radiographic and/or pathologic means, will identify two cohorts; responders and nonresponders.Gene expression profiling will then be performed on pre-treatment specimens to identify signatures that predict for chemotherapy sensitivity or resistance.

The target enrollment is 45 patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dose-Dense Induction/Neoadjuvant Chemotherapy in the Treatment of Patients With Locally Advanced Non-Small Cell Lung Cancer With Additional Genomic Analyses to Identify Signatures Predictive of Chemotherapy Response.
• Study Start Date: May 2006
• Actual Primary Completion Date: October 2009
• Actual Study Completion Date: January 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Induction Chemotherapy; Cisplatin 75mg/m2 IV days 1, 15, 29; Docetaxel 75mg/m2 IV days 1, 15, 29; and Pegfilgrastim 6mg SC day 2, 16, 30	Drug: cisplatin; Other Name: Platinol; Drug: Docetaxel; Other Name: Taxotere; Drug: Pegfilgrastim; Other Name: Neulasta

Outcome Measures

Primary Outcome Measures :

1. Induction Response [ Time Frame: Between 2 and 3 weeks after induction ]
   Response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Response is defined as the number patients with a Complete Response (CR), disappearance of all target lesions, or a Partial Response (PR), at least a 30% decrease in the sum of the longest diameter (LD) of target lesions.
2. Differential Gene Expression Between Responsive and Resistant Tumor Treated With Dose-dense Therapy [ Time Frame: at the end of the study, estimated 2.5 years ]

Secondary Outcome Measures :

1. Number of Grade III/IV Hematologic Adverse Events [ Time Frame: During induction chemotherapy, approximately 6 weeks ]
2. Number of Grade III/IV Non-hematologic Adverse Events [ Time Frame: During induction chemotherapy, approximately 6 weeks ]
3. Number of Patients Who Were Able to Maintain Hemoglobin Between 11-13 g/dL During Induction [ Time Frame: During induction, approximately 6 weeks ]
4. Overall Survival [ Time Frame: Approximately 10 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with documented stage III NSCLC (IIIA or IIIB, without malignant pleural/pericardial effusion) are eligible for enrollment if they are considered appropriate for treatment with chemotherapy, radiation, or surgery;
• IIIA: T1-3 N2 M0, T3 N1 M0
• IIIB: T4 N0-2 M0, T 1-4 N3 M0
• Measurable or evaluable disease
• Previously untreated with chemotherapy or radiotherapy for lung cancer;
• No brain metastases;
• No prior XRT
• Performance status 0-2
• ≥18 years of age
• Informed Consent
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Bilirubin ≤ 1.5 x upper limit of normal for the institution (ULN)
• SGOT and SGPT ≤ 2.5 x ULN for the institution
• Creatinine ≤ 1.6 mg/dL
• Hemoglobin ≥ 8.0 g/dL
• Peripheral neuropathy ≤ grade 1

Exclusion Criteria:

• Known sensitivity to E. coli derived products (e.g. Filgrastim, HUMULIN® insulin, L-asparaginase, HUMATROPE® Growth Hormone, INTRON® A);
• Use of IV systemic antibiotics within 72 hours prior to chemotherapy;
• Known HIV infection
• Lithium or cytokines within 2 weeks prior of entry
• Additional concurrent investigational drugs
• History of myelodysplastic syndrome
• Pregnant, nursing or having unprotected sex
• Not available for follow-up assessment
• Unable to comply with protocol procedures
• Illnesses that may compromise ability to give informed consent.
• Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80.

Contacts and Locations

Locations

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

Sanofi

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02157116
• Other Study ID Numbers: Pro00004682
• First Posted: June 5, 2014
• Results First Posted: July 4, 2014
• Last Update Posted: July 4, 2014
• Last Verified: June 2014

Keywords provided by Duke University:

Dose-Dense Chemotherapy

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Docetaxel; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action