Clinical trial NCT00544648: Ph I/II Nab-Paclitaxel & Carboplatin w/Concurrent Radiation Therapy for Unresectable Stg III NSCLC
Official title: A Phase I/II Study of Nab-Paclitaxel and Carboplatin With Concurrent Radiation Therapy for Unresectable Stage III Non-Small-Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Keywords: stage IV non-small cell lung cancer
stage IIIB non-small cell lung cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-16
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: RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) may make tumor cells more sensitive to radiation therapy. Giving nab-paclitaxel together with radiation therapy and carboplatin may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving nab-paclitaxel together with carboplatin and radiation therapy and to see how well it works in treating patients with stage III non-small-cell lung cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerated dose of nab-paclitaxel when combined concurrently with carboplatin and radiation followed by two courses of nab-paclitaxel carboplatin as consolidation. (Phase I)
* To evaluate the progression-free survival in patients with stage III unresectable non-small cell lung cancer treated with nab-paclitaxel, carboplatin, and radiotherapy followed by two courses of nab-paclitaxel with carboplatin as consolidation. (Phase II)

Secondary

* To assess safety and tolerability and identify dose-limiting toxicities in patients receiving nab-paclitaxel combined concurrently with carboplatin and radiotherapy. (Phase I)
* To assess progression-free survival, response rates, and survival. (Phase I)
* To assess overall survival and response rates in all patients treated on this study. (Phase II)
* To assess the safety and tolerability of patients receiving nab-paclitaxel combined concurrently with carboplatin and radiotherapy followed by two courses of nab-paclitaxel/carboplatin as consolidation. (Phase II) OUTLINE: This is a multicenter study.
* Phase I:

  * Concurrent chemoradiotherapy: Patients receive escalating doses of nab-paclitaxel IV over 30 minutes and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43. They also receive conformal radiotherapy once daily 5 days a week on days 1-5 in weeks 1-7. Patients are evaluated between weeks 8-10. Patients with disease progression are removed from study. Patients with stable disease, partial response, or complete response proceed to consolidation chemotherapy 3 weeks after completion of chemoradiotherapy.
  * Consolidation chemotherapy: Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats ever 21 days for up to 2 courses.
* Phase II: Patients receive concurrent chemoradiotherapy at the Maximum Tolerated Dose (MTD) of nab-paclitaxel followed by consolidation chemotherapy as in phase I.

After completion of study treatment, patients are followed at 2 months, every 3 months for 2 years, every 4 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 98 patients (15 patients for phase I and 83 patients for phase II) will be accrued for this study.

Eligibility criteria: Inclusion Criteria for Phase I and Phase II Patients:

* Patients must voluntarily sign and date an informed consent before the initiation of any study procedures
* Patients must have non-metastatic, inoperable, Stage IIIA or IIIB histologically or cytologically documented NSCLC without evidence of malignant pleural effusion
* Patients must not have received any prior systemic chemotherapy, thoracic radiotherapy or surgical resection for treatment of NSCLC
* Patients must have at least one site of unidirectionally measurable disease as defined by Response Evaluation in Solid Tumors (RECIST) criteria
* Patients must be ≥ 3 weeks from a formal exploratory thoracotomy
* Patients must have a Radiation Oncology and Medical Oncology consult and approval prior to study entry
* Patients must be ≥ 18 years of age
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Women of childbearing potential must have a negative baseline serum pregnancy or a negative urine pregnancy test within 7 days prior to Week 1, Day 1 and must not be breast feeding.
* Women of childbearing potential and men with a sexual partner of child bearing potential must use an effective method of contraception beginning prior to study entry, for the duration of the study participation and for a minimum of 3 months after the last dose of chemotherapy.
* Patients must have adequate hepatic, renal, lung and bone marrow function as defined below:

  * Absolute neutrophil count (ANC) ≥1,500/mm3
  * Hemoglobin ≥ 9.0 gm/dL
  * Serum Creatinine ≤1.5mg/dl
  * Platelets \> 100,000/mm3
  * Total bilirubin ≤ upper limit of normal
  * AST and ALT \< 2.5 X upper limit of normal
  * Alkaline phosphatase \< 2.5 X upper limit of normal
  * Calculated CrCl \> 45 ml/min (via Cockroft-Gault formula)
  * Forced expiratory volume in 1 second (FEV 1) \> 800 ml

Exclusion Criteria for Phase I and Phase II Patients:

* Known hypersensitivity to carboplatin or nab-paclitaxel
* Peripheral neuropathy Grade ≥ 2
* Wet stage IIIB (documented malignant pleural effusion) or stage IV NSCLC
* Previous chemotherapy or radiation therapy to the chest
* Any concomitant malignancy or brain metastasis
* Any uncontrolled, clinically significant medical or psychiatric disorder
* Pregnant or nursing women
* A greater than or equal to 10% weight loss over the past 3 months

Primary outcomes:
measure: Maximum Tolerated Dose of Nab-paclitaxel When Combined Concurrently With Carboplatin and Radiation (Phase I)
timeFrame: 7 weeks
measure: Progression-free Survival (Phase II)
timeFrame: On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years)
Secondary outcomes:
measure: Progression-free Survival (Phase I)
timeFrame: On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years)
measure: Overall Survival (Phase I)
timeFrame: On-study date to date of death from any cause (assessed up to 2 years)
measure: Response (Phase I)
timeFrame: On-treatment date to date of progressive disease (assessed up to 2 years)
measure: Number of Patients With Each Worst Grade Toxicity (Phase I)
timeFrame: On-study date to 30 days following final dose of study drug
measure: Overall Survival (Phase II)
timeFrame: Time Frame: date on study to date of death from any cause or last known date alive
measure: Number of Patients With Each Worst Grade Toxicity (Phase II)
timeFrame: at 16 weeks
measure: Response (Phase II)
timeFrame: On-treatment date to date of progressive disease (assessed up to 2 years)
Other outcomes:
measure: Secreted Protein Acidic and Rich in Cysteine (SPARC) Gene Expression
timeFrame: On receipt of tumor tissue blocks
Locations:
city: Paducah
country: United States
facility: Purchase Cancer Group - Paducah
state: Kentucky
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Chattanooga
country: United States
facility: Erlanger Cancer Center at Erlanger Hospital - Baroness
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Franklin
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Vicki Keedy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lammers PE, Lu B, Horn L, Shyr Y, Keedy V. nab-Paclitaxel in Combination With Weekly Carboplatin With Concurrent Radiotherapy in Stage III Non-Small Cell Lung Cancer. Oncologist. 2015 May;20(5):491-2. doi: 10.1634/theoncologist.2015-0030. Epub 2015 Apr 6.