Clinical trial NCT02157116: Dose-Dense Induction/Neoadjuvant Chemotherapy in Locally Advanced Non-Small Cell Lung Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Dose-Dense Chemotherapy
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2014-06-05
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Induction Response
timeFrame: Between 2 and 3 weeks after induction
measure: Differential Gene Expression Between Responsive and Resistant Tumor Treated With Dose-dense Therapy
timeFrame: at the end of the study, estimated 2.5 years
Secondary outcomes:
measure: Number of Grade III/IV Hematologic Adverse Events
timeFrame: During induction chemotherapy, approximately 6 weeks
measure: Number of Grade III/IV Non-hematologic Adverse Events
timeFrame: During induction chemotherapy, approximately 6 weeks
measure: Number of Patients Who Were Able to Maintain Hemoglobin Between 11-13 g/dL During Induction
timeFrame: During induction, approximately 6 weeks
measure: Overall Survival
timeFrame: Approximately 10 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
References: