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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00728845
• Other study ID #: CDR0000600241
• Secondary ID: P30CA072720CINJ-
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: August 5, 2008
• Last updated: September 18, 2013
• Start date: June 2008
• Est. completion date: December 2016

Study information

• Verified date: September 2013
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, carboplatin, and paclitaxel and work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving hydroxychloroquine together with carboplatin, paclitaxel and bevacizumab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of hydroxychloroquine when given together with carboplatin, paclitaxel, and bevacizumab and to see how well they work in treating patients with recurrent advanced non-small cell lung cancer.

Description:

OBJECTIVES:

Primary

• 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)

• To assess the antitumor activity, as measured by tumor response rate, of this regimen in these patients. (Phase II)

Secondary

• To measure time to progression, progression-free survival, and overall survival of these patients.

• To assess the incidence of toxicity of this regimen in these patients.

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.

Other known NCT identifiers

• NCT00933803

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: December 2016
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Biological:
• bevacizumab
Only patients eligible for bevacizumab will receive bevacizumab. Dose is at 15 mg/kg on day 1 of each cycle.

Drug:
• carboplatin
Carboplatin will be given at AUC = 6 by IV over 15-30 minutes on Day 1 immediately following paclitaxel
• hydroxychloroquine
200 mg orally BID (total daily dose of 400 mg)
• paclitaxel
Dose of 200 mg/m2 IV on day 1 of each cycle

Locations

Country	Name	City	State
United States	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
University of Medicine and Dentistry of New Jersey	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended Phase II Dose of Hydroxychloroquine and Carboplatin When Administered With Paclitaxel and Bevacizumab (Phase I)		Phase I portion of study	No
Primary	Overall Response (Phase II)		Treatment start date to date of best response	No
Secondary	Time to Progression (Phase II)		Treatment start date and date of progression	No
Secondary	Progression-free Survival at 1 Year (Phase II)		Treatment start date to 1 year	No
Secondary	Overall Survival (Phase II)		Treatment start date to date of death	No

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database