Clinical trial NCT01557959: Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Official title: Phase II Study of Sequential Dose-Dense Chemotherapy and Dose-Intense Erlotinib for the Initial Treatment of Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Lung
Adenosquamous Cell Lung Cancer
Bronchoalveolar Cell Lung Cancer
Large Cell Lung Cancer
Non-small Cell Lung Cancer
Recurrent Non-small Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: OSI Pharmaceuticals
First posted: 2012-03-20
Enrollment: 45
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: This phase II trial is studying how well docetaxel given together with cisplatin and pegfilgrastim followed by erlotinib hydrochloride works in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dose-dense combination chemotherapy together with pegfilgrastim and erlotinib hydrochloride may kill more tumor cells

Detailed description: PRIMARY OBJECTIVES:

I. To determine if this regimen improves the time-to-progression for patients with advanced non-small cell lung cancer (NSCLC) compared to historical controls.

SECONDARY OBJECTIVES:

I. To assess response rate and median survival. II. To evaluate tumor biomarkers that could predict response and survival for patients treated with this regimen including endothelial growth factor receptor (EGFR) expression, EGFR Fluorescence in situ hybridization (FISH), and k-ras mutations.

III. To evaluate genetic polymorphisms as markers of response and survival for patients treated with this regimen including polymorphisms in XPD, XRCC1, XRCC3, and cyclin D1.

OUTLINE:

Patients receive docetaxel intravenously (IV) over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive erlotinib hydrochloride orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and every 6 months for 2 years.

Eligibility criteria: Inclusion Criteria:

* Histologic Documentation: Either histologic or cytologic documentation of non-small cell carcinoma (NSCLC) is necessary, and the following diagnostic categories are acceptable: squamous carcinoma, basaloid carcinoma, adenocarcinoma, bronchioloalveolar carcinoma, adenosquamous carcinoma, large cell carcinoma (not neuroendocrine), sarcomatoid carcinoma, and non-small cell carcinoma not otherwise specified (NOS); histologic or cytologic documentation of recurrence is required in patients who were previously completely resected
* Advanced Disease: Stage IIIB because of malignant pleural or pericardial effusion or stage IV disease
* Patients must be ineligible for Avastin or decline treatment with Avastin
* Prior Treatment: No prior chemotherapy or treatment with an EGFR inhibitor is allowed; brain metastasis must be under control (patient neurologically stable)
* All Patients must have Measurable or Non-Measurable Disease: measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; the longest diameter of measurable lesions must be \>= 20 mm with conventional techniques or \>= 10 mm with spiral computed tomography (CT) scan; non-measurable disease includes the following:

  * Bone lesions
  * Brain metastasis or leptomeningeal disease
  * Ascites
  * Pleural/pericardial effusion
  * Abdominal masses that are not confirmed and followed by imaging techniques
  * Cystic lesions
  * Tumor lesions situated in a previously irradiated area

    * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
    * Granulocytes \>= 1,500/ul
    * Platelets \>= 100,000/ul
    * Creatinine =\< upper limit of normal (ULN)
    * Bilirubin =\< 1.5 mg/dl
    * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 1.5 x ULN
    * Alkaline (Alk.) phosphatase (phos.) =\< 2.5 x ULN
* Patients must provide verbal and written informed consent to participate in the study

Exclusion Criteria:

* Patients who are pregnant or nursing because of significant risk to the fetus/infant
* Patients with neuropathy \>= grade 2
* Patients with a psychiatric illness which would prevent the patient from giving informed consent
* Patients who are unable to take oral medications
* Women with child-bearing potential or men who are sexual partners of women with child-bearing potential who are not willing to practice adequate contraceptive measures

Primary outcomes:
measure: Time to Progression
timeFrame: 2 years
Secondary outcomes:
measure: Response Rate Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood
timeFrame: 2 years
measure: Median Survival Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood
timeFrame: 2 years
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: William Petty
role: PRINCIPAL_INVESTIGATOR
References:
citation: Petty WJ, Laudadio J, Brautnick L, Lovato J, Dotson T, Streer NP, Weaver KE, Miller AA. Phase II trial of dose-dense chemotherapy followed by dose-intense erlotinib for patients with newly diagnosed metastatic non-small cell lung cancer. Int J Oncol. 2013 Dec;43(6):2057-63. doi: 10.3892/ijo.2013.2122. Epub 2013 Oct 3.