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

This study has been terminated.
(Slow accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey ( University of Medicine and Dentistry of New Jersey )
ClinicalTrials.gov Identifier:
NCT00728845
First received: August 5, 2008
Last updated: September 18, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Biological: bevacizumab
Drug: carboplatin
Drug: hydroxychloroquine
Drug: paclitaxel
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Recommended Phase II Dose of Hydroxychloroquine and Carboplatin When Administered With Paclitaxel and Bevacizumab (Phase I) [ Time Frame: Phase I portion of study ] [ Designated as safety issue: No ]
  • Overall Response (Phase II) [ Time Frame: Treatment start date to date of best response ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to Progression (Phase II) [ Time Frame: Treatment start date and date of progression ] [ Designated as safety issue: No ]
  • Progression-free Survival at 1 Year (Phase II) [ Time Frame: Treatment start date to 1 year ] [ Designated as safety issue: No ]
  • Overall Survival (Phase II) [ Time Frame: Treatment start date to date of death ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: June 2008
Estimated Study Completion Date: December 2016
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hydroxychloroquine, Carboplatin, Paclitaxel, Bevacizumab
Cohort 1: Bevacizumab Eligible Patients All on Day 1 Paclitaxel 200mg/m2 IV over 3 hours Carboplatin AUC= 6 IV over 15-30 min Bevacizumab 15 mg/kg IV over 90 min for PLUS Hydroxychloroquine 200 mg PO BID Cycles every 3 weeks for 4-6 Cycles
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
Drug: hydroxychloroquine
200 mg orally BID (total daily dose of 400 mg)
Drug: paclitaxel
Dose of 200 mg/m2 IV on day 1 of each cycle
Experimental: Hydroxychloroquine, Carboplatin, Paclitaxel
Cohort 2: Bevacizumab Ineligible Patients All on Day 1 Paclitaxel 200mg/m2 IV over 3 hours Carboplatin AUC= 6 IV over 15-30 min PLUS Hydroxychloroquine 200 mg PO BID Cycles every 3 weeks for 4-6 Cycles
Drug: carboplatin
Carboplatin will be given at AUC = 6 by IV over 15-30 minutes on Day 1 immediately following paclitaxel
Drug: hydroxychloroquine
200 mg orally BID (total daily dose of 400 mg)
Drug: paclitaxel
Dose of 200 mg/m2 IV on day 1 of each cycle

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00728845

Locations
United States, New Jersey
Cancer Institute of New Jersey at Hamilton
Hamilton, New Jersey, United States, 08690
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
University of Medicine and Dentistry of New Jersey
Investigators
Principal Investigator: Joseph Aisner, MD Rutgers Cancer Institute of New Jersey
  More Information

Additional Information:
No publications provided

Responsible Party: Rutgers, The State University of New Jersey ( University of Medicine and Dentistry of New Jersey )
ClinicalTrials.gov Identifier: NCT00728845     History of Changes
Other Study ID Numbers: CDR0000600241, P30CA072720, CINJ-030801
Study First Received: August 5, 2008
Results First Received: September 18, 2013
Last Updated: September 18, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Rutgers, The State University of New Jersey:
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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Bevacizumab
Carboplatin
Hydroxychloroquine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on September 29, 2014