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(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

Phase 1/Phase 2
18 Years
Not Enrolling
Lung Cancer

Thank you

Trial Information

(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



- 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)


- 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.

Inclusion Criteria


- 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


- 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


- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

Phase I portion of study

Safety Issue:


Principal Investigator

Joseph Aisner, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey


United States: Food and Drug Administration

Study ID:




Start Date:

June 2008

Completion Date:

December 2011

Related Keywords:

  • Lung Cancer
  • adenocarcinoma of the lung
  • large cell lung cancer
  • recurrent non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Cancer Institute of New Jersey at HamiltonHamilton, New Jersey  08690
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903