Hydroxychloroquine + Carboplatin, Paclitaxel and Bevacizumab in Non-Small Cell Lung Cancer (NSCLC)

This study is ongoing, but not recruiting participants.
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:
NCT00933803
First received: June 16, 2008
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to examine the combination of one standard treatment for lung cancer plus an additional drug, hydroxychloroquine. The standard treatment for lung cancer being used includes 2 chemotherapy drugs, called paclitaxel and carboplatin, plus a drug that targets blood vessels, called bevacizumab (also known as avastin).

Recent medical science suggests that the investigators may be able to make anticancer therapy work better if they can block autophagy. Autophagy is a cellular process that helps normal cells live through times of stress, for example during times of starvation. Studies suggest that cancer cells may take advantage of autophagy to survive longer and to survive despite treatment with chemotherapy. The investigators want to know if blocking autophagy while giving standard treatment for lung cancer will improve the treatment of lung cancer. The investigators will use hydroxychloroquine, which blocks autophagy, in addition to standard treatment in the treatment of lung cancer.

The primary endpoint is to determine the recommended Phase II dose of paclitaxel, carboplatin, bevacizumab in combination with hydroxychloroquine in patients with advanced or recurrent NSCLC.

The primary objective of this study is to assess the antitumor activity, as measured by tumor response rate, of paclitaxel, carboplatin, bevacizumab and hydroxychloroquine in patients with advanced or recurrent NSCLC cancer.

Secondary Endpoint(s):

  • To measure time to progression, percent one-year survival and overall survival.
  • To assess toxicity of this regimen.
  • To develop pharmacodynamic markers for autophagy detection in patient specimens.
  • To characterize the effects of hydroxychloroquine on autophagy in patients in vivo.

Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Paclitaxel
Drug: Carboplatin
Drug: Hydroxychloroquine
Drug: Bevacizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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:
  • The primary objective of this study is to assess the antitumor activity, as measured by tumor response rate, of paclitaxel, carboplatin, bevacizumab and hydroxychloroquine in patients with advanced or recurrent NSCLC cancer. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • measure time to progression, % 1 yr survival; overall survival. assess toxicity of regimen. develop pharmacodynamic markers for autophagy detection in patient specimens and to characterize the effects of hydroxychloroquine on autophagy in pts in vivo. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Enrollment: 8
Study Start Date: June 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
combination of paclitaxel at 200 mg/m2 intravenously over 3 hours on Day 1; followed by carboplatin AUC = X intravenously over 15-30 minutes on Day 1 (dose to be determined [TBD] during the Phase I portion); followed by bevacizumab at 15 mg/kg intravenously (initial infusion over 90 minutes) on Day 1; and hydroxychloroquine orally (dose TBD during the Phase I portion) Days 1-21. Chemotherapy will be repeated every 21 days for a total of 4 cycles. Patients will then continue to receive bevacizumab every 21 days and hydroxychloroquine daily up to 1 year until evidence of disease progression or unacceptable toxicity.After baseline evaluation, tumor response will be evaluated every 2 cycles (6 weeks) of therapy. Responses will be assessed using RECIST criteria. Patient survival will be followed every 6 months after initiation of treatment.
Drug: Paclitaxel
200 mg/m2 intravenously over 3 hours on Day 1
Other Name: Taxol®
Drug: Carboplatin
intravenously over 15-30 minutes on Day 1 (dose to be determined [TBD] during the Phase I portion
Other Name: Paraplatin®
Drug: Hydroxychloroquine
(dose TBD during the Phase I portion) Days 1-21
Drug: Bevacizumab
15 mg/kg intravenously (initial infusion over 90 minutes)
Other Name: Avastin®

  Eligibility

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

Inclusion Criteria:

  • Signed a protocol-specific informed consent.
  • 18 years of age or older.
  • ECOG Performance Status 0 or 1.
  • Histologically or cytologically confirmed non-small cell lung cancer EXCEPT squamous cell carcinoma. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirate or biopsy. Sputum cytology alone is not sufficient.
  • Advanced stage NSCLC (stage IIIB with malignant pleural effusion, or stage IV, or recurrent disease).
  • Measurable disease according to RECIST criteria.
  • No known CNS metastases. A head CT or brain MRI is required within 28 days of enrollment.
  • No prior cytotoxic chemotherapy or targeted therapy in the advanced or metastatic setting. Post-operative adjuvant therapy for previously resected NSCLC is allowed as long as the last dose was given greater than 1 year before study entry, and there is current evidence of disease progression.
  • Prior radiation to sites other than the brain is allowed, if completed at least 2 weeks prior to treatment and provided that all radiation-related toxicities have resolved to ≤ Grade 1.
  • No active malignancy other than NSCLC. Patients with a history of basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast within the past 3 years must have been treated with curative intent. Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for > 3 years.
  • Adequate organ function
  • No history of gross hemoptysis (defined as bright red blood of a half-teaspoon or more) within 3 months prior to enrollment.
  • None of the following conditions within 6 months prior to enrollment: myocardial infarction, stroke or symptomatic peripheral vascular disease.
  • No major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, or anticipate the need for such while on active treatment. Placement of vascular access device is not considered major surgery, but the incision must have healed before initiation of treatment.
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment.
  • No serious non-healing wound, ulcer or bone fracture.
  • Patients must have a systolic blood pressure ≤ 150 mm Hg and diastolic blood pressure ≤ 100 mm Hg (the use of antihypertensive medications to achieve these goals is allowed).
  • Patients must not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2 (see Appendix C).
  • No history of significant vascular disease (eg aortic aneurysm).
  • Patients must not have psoriasis or porphyria.
  • No known hypersensitivity to 4-aminoquinoline compound.
  • Patients must not have retinal or visual field changes from prior 4-aminoquinoline compound use.
  • Patients must not have known G-6P deficiency.
  • No current or recent (within 28 days of enrollment) full dose anticoagulants or thrombolytic agents.
  • No know bleeding diathesis or coagulopathy.
  • No known GI pathology that would interfere with drug bioavailability.
  • No peripheral or sensory neuropathy > Grade 1 at study entry.
  • No known prior hypersensitivity to carboplatin, paclitaxel, bevacizumab or hydroxychloroquine or any of their components.
  • No ongoing or active infection at study entry.
  • Patients must not be receiving treatment for rheumatoid arthritis or systemic lupus erythematosus.
  • Patients must not have HIV or be taking HAART therapy.
  • Patients must not have a history of any condition (social or medical) that, in the opinion of the Investigator, might interfere with the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient.
  • Women must NOT be pregnant or breastfeeding.
  • Women must :

    • Have a negative serum or urine pregnancy test within 7 days prior to study entry if she is a woman of child-bearing potential
    • Be at least one year post-menopausal
    • Be surgically sterile
  • Patients of childbearing or child fathering potential must be willing to use an acceptable method of birth control prior to study entry and for the duration of the study. Acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence.
  • Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00933803

Locations
United States, New Jersey
The Cancer institute of New jersey at Hamilton
Hamilton, New Jersey, United States, 08690
Mountainside Hospital
Montclair, New Jersey, United States, 07042
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
New Jersey Medical School-University Hospital Cancer Center
Newark, New Jersey, United States, 07103
Cooper Cancer Institute
Vorhees, New Jersey, United States, 08043
Sponsors and Collaborators
University of Medicine and Dentistry of New Jersey
Investigators
Principal Investigator: Joseph Aisner, MD CINJ/UMDNJ
  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: NCT00933803     History of Changes
Other Study ID Numbers: 030801, NJ 1508, 0220080123, 030801
Study First Received: June 16, 2008
Last Updated: August 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Rutgers, The State University of New Jersey:
NSCLC
advanced/recurrent 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
Hydroxychloroquine
Bevacizumab
Carboplatin
Paclitaxel
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on August 28, 2014