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

Alternate Title

Hydroxychloroquine, Carboplatin, Paclitaxel, and Bevacizumab in Treating Patients With Recurrent Advanced Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Active	18 and over	NCI	CINJ-030801 030801, NCT00728845

Objectives

Primary

1. To determine the recommended phase II dose of hydroxychloroquine and carboplatin in combination with paclitaxel and bevacizumab in patients with advanced recurrent non-small cell lung cancer. (Phase I)
2. To assess the antitumor activity, as measured by tumor response rate, of this regimen in these patients. (Phase II)

Secondary

1. To measure time to progression, progression-free survival, and overall survival of these patients.
2. To assess the incidence of toxicity of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed advanced non-small cell lung cancer, meeting the following criteria:
  • Recurrent disease
  • No component of squamous cell carcinoma
  • Mixed tumors will be categorized by predominant cell type
    • No mixed histology with small cell component



• Diagnosis established on metastatic tumor aspirate or biopsy (not sputum cytology alone) and meets 1 of the following staging criteria:
  • Stage IIIB disease with malignant pleural effusion
  • Stage IV disease



• Measurable disease



• More than 1 year since post-operative adjuvant therapy for previously resected non-small cell lung cancer with evidence of disease progression



• No known CNS metastases by CT scan or brain MRI within the past 28 days

Prior/Concurrent Therapy:

• See Disease Characteristics
• At least 2 weeks since prior radiation to sites other than the brain, and recovered to ≤ grade 1
• At least 28 days since prior and no concurrent full-dose anticoagulants or thrombolytic agents
• At least 28 days since prior major surgical procedure or open biopsy and no anticipated need for such during study therapy
  • Vascular access device placement with wound recovery allowed before study
• No prior cytotoxic chemotherapy or targeted therapy in the advanced or metastatic setting
• No concurrent treatment for rheumatoid arthritis or systemic lupus erythematosus
• No concurrent combination antiretroviral therapy
• No concurrent hydroxychloroquine for treatment or prophylaxis of malaria
• No concurrent aurothioglucose
• No other concurrent investigational or commercial agent or therapy for this malignancy

Patient Characteristics:

• ECOG performance status 0-1
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 2 times ULN and no other liver function test abnormality in patients with Gilbert disease)
• AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• INR ≤ 1.5 and aPTT normal
• Urine protein:creatinine ratio < 1.0 OR urine protein ratio < 1,000 mg by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No psoriasis or porphyria
• No HIV positivity
• No significant traumatic injury within the past 28 days
• No serious non-healing wound, ulcer, or bone fracture
• No peripheral or sensory neuropathy > grade 1
• No hypertension that cannot be controlled by antihypertensive medication (i.e., blood pressure > 150/100 mm Hg despite optimal medical therapy)
• No cardiovascular disease, including any of the following:
  • Unstable angina
  • New York Heart Association class II-IV congestive heart failure
  • History of significant vascular disease (e.g., aortic aneurysm)
  • Symptomatic peripheral vascular disease within the past 6 months
  • Myocardial infarction within the past 6 months
  • Stroke within the past 6 months
• No other active malignancy within the past 3 years, except curatively treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast, or other curatively treated malignancy with no evidence of disease > 3 years
• No retinal or visual field changes from prior 4-aminoquinoline compound therapy
• No known hypersensitivity to 4-aminoquinoline compound
• No known glucose-6-phosphate (G-6P) deficiency
• No known bleeding diathesis or coagulopathy
• No known gastrointestinal pathology that would interfere with drug bioavailability
• No known prior hypersensitivity to carboplatin, paclitaxel, bevacizumab, hydroxychloroquine, or any of their components
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No history of gross hemoptysis (i.e., bright red blood of a ½ teaspoon or more) within the past 3 months
• No history of any social or medical condition that, in the investigator's opinion, might interfere with the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient

Expected Enrollment

Outcomes

Recommended phase II dose of hydroxychloroquine and carboplatin when administered with paclitaxel and bevacizumab (phase I)
Overall response (phase II)

Time to progression (phase II)
Progression-free survival at 1 year (phase II)
Overall survival (phase II)

Outline

This is a multicenter study. This is a phase I, dose-escalation study of carboplatin and hydroxychloroquine followed by a phase II study.

Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 90 minutes on day 1 and oral hydroxychloroquine on days 1-21. Treatment repeats every 21 days for a total of 4 courses. Patients then receive bevacizumab IV over 30-90 minutes every 21 days and oral hydroxychloroquine daily for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 6 months.

Trial Contact Information

Trial Lead Organizations

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Mika Sovak, MD, PhD, Principal investigator		Ph: 732-235-8078 Email: sovakmi@umdnj.edu

U.S.A.
New Jersey
	Hamilton
	Cancer Institute of New Jersey at Hamilton
		Clinical Trials Office - Cancer Institute of New Jersey at Hamilton	Ph:  609-631-6946
	New Brunswick
	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
		Clinical Trials Office - Cancer Institute of New Jersey	Ph:  732-235-8675

Registry Information
Official Title		(NJ 1508) Modulation of Autophagy with Hydroxychloroquine in Combination with Carboplatin, Paclitaxel and Bevacizumab in Patients with Advanced/Recurrent Non-Small Cell Lung Cancer - A Phase I/II Study
Trial Start Date		2008-06-16
Trial Completion Date		2011-08-09 (estimated)
Registered in ClinicalTrials.gov		NCT00728845
Date Submitted to PDQ		2008-07-14
Information Last Verified		2008-11-06
NCI Grant/Contract Number		CA72720

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