Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Carboplatin, and Radiation Therapy in Treating Patients With Stage III Non-Small-Cell Lung Cancer That Cannot Be Removed by Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Active 18 and over NCI VU-VICC-THO-0746 VICC-THO-0746, NCT00544648

Objectives

Primary

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

Secondary

1. To assess safety and tolerability and identify dose-limiting toxicities in patients receiving paclitaxel albumin-stabilized nanoparticle formulation combined concurrently with carboplatin and radiotherapy. (Phase I)
2. To assess progression-free survival, response rates, and survival. (Phase I)
3. To assess overall survival and response rates in all patients treated on this study. (Phase II)
4. To assess the safety and tolerability of patients receiving paclitaxel albumin-stabilized nanoparticle formulation combined concurrently with carboplatin and radiotherapy followed by two courses of paclitaxel albumin-stabilized nanoparticle formulation/carboplatin as consolidation. (Phase II)
5. To analyze tumor specimens for the secreted protein acidic and rich in cysteine (SPARC) gene expression.

Entry Criteria

Disease Characteristics:

Inclusion criteria:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting all of the following criteria:
  • Non-metastatic, inoperable disease
  • Stage IIIA or IIIB disease



• Must have ≥ 1 site of unidirectionally measurable disease



• No evidence of malignant pleural effusion

Exclusion criteria:

• Wet stage IIIB or stage IV NSCLC



• Brain metastasis

Prior/Concurrent Therapy:

• No prior systemic chemotherapy, thoracic radiotherapy, or surgical resection for treatment of NSCLC
• More than 3 weeks since prior exploratory thoracotomy
• No prior chemotherapy or radiotherapy to the chest
• No other concurrent chemotherapy, immunotherapy, or antitumor hormonal therapy

Patient Characteristics:

Inclusion criteria:

• ECOG performance status 0-1
• ANC ≥ 1,500/mm³
• Hemoglobin ≥ 9.0 g/dL
• Creatinine ≤ 1.5 mg/dL or creatinine clearance > 45 mL/min
• Platelet count > 100,000/mm³
• Total bilirubin normal
• AST and ALT ≤ 2.5 x upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 x ULN
• FEV₁ > 800 mL
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for at least 3 months after completion of study therapy

Exclusion criteria:

• Known hypersensitivity to carboplatin or paclitaxel albumin-stabilized nanoparticle formulation
• Peripheral neuropathy ≥ grade 2
• Any uncontrolled, clinically significant medical or psychiatric disorder
• Pregnant or nursing women
• At least 10% weight loss over the past 3 months
• Any concurrent malignancy

Expected Enrollment

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

Outcomes

Maximum tolerated dose (phase I)
Progression-free survival (phase II)

Progression-free survival (phase I)
Survival (phase I)
Response rate (phase I)
Secreted protein acidic and rich in cysteine (SPARC) gene expression
Overall survival (phase II)
Safety and tolerability
Dose-limiting toxicity (phase I)

Outline

This is a multicenter study.

• Phase I:
  • Concurrent chemoradiotherapy: Patients receive escalating doses of paclitaxel albumin-stabilized nanoparticle formulation (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 MTD of nab-paclitaxel followed by consolidation chemotherapy as in phase I.

Paraffin embedded blocks from previously performed biopsies or resections from consenting patients are obtained for SPARC gene expression.

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.

Trial Contact Information

Trial Lead Organizations

Vanderbilt-Ingram Cancer Center

Alan Sandler, MD, Principal investigator		Ph: 800-811-8480 Email: alan.sandler@vanderbilt.edu
Vicki Keedy, MD, Principal investigator		Ph: 800-811-8480
Bo Lu, MD, PhD, Principal investigator		Ph: 800-811-8480

U.S.A.
Kentucky
	Owensboro
	Mitchell Memorial Cancer Center at Owensboro Medical Health System
		Dattatraya Prajapati	Ph:  270-688-1900
	Paducah
	Purchase Cancer Group - Paducah
		Contact Person	Ph:  270-554-0011 800-866-4465
Tennessee
	Chattanooga
	Erlanger Cancer Center at Erlanger Hospital - Baroness
		Clinical Trials Office - Erlanger Cancer Center	Ph:  423-778-6947
	Nashville
	Vanderbilt-Ingram Cancer Center
		Clinical Trials Office - Vanderbilt-Ingram Cancer Center	Ph:  1-800-811-8480;
	Vanderbilt-Ingram Cancer Center - Cool Springs
		Vicki Keedy	Ph:  615-322-4967
	Vanderbilt-Ingram Cancer Center at Franklin
		Vicki Keedy	Ph:  615-591-9890

Registry Information
Official Title		VICC THO 0746 - A Phase I/II Study of Nab-Paclitaxel and Carboplatin with Concurrent Radiation Therapy for Unresectable Stage III Non-Small-Cell Lung Cancer (NSCLC)
Trial Start Date		2007-11-05
Trial Completion Date		2010-06-30 (estimated)
Registered in ClinicalTrials.gov		NCT00544648
Date Submitted to PDQ		2007-10-03
Information Last Verified		2008-10-01
NCI Grant/Contract Number		CA68485