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

NCT00728845 | Terminated Phase 1 Results

• 3 other identifiers: CDR0000600241P30CA072720CINJ-030801
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Recommended Phase II Dose of Hydroxychloroquine and Carboplatin When Administered With Paclitaxel and Bevacizumab (Phase I)

  Followed for the duration of the phase 1 treatment, an average of 18 weeks

• Overall Response (Phase II)

  Treatment start date to date of best response

Secondary Outcomes (3)

• Time to Progression (Phase II)

  Treatment start date and date of progression

• Progression-free Survival at 1 Year (Phase II)

  Treatment start date to 1 year

• Overall Survival (Phase II)

  Treatment start date to date of death

Study Arms (2)

Hydroxychloroquine, Carboplatin, Paclitaxel, Bevacizumab

EXPERIMENTAL

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; Drug: carboplatin; Drug: hydroxychloroquine; Drug: paclitaxel

Hydroxychloroquine, Carboplatin, Paclitaxel

EXPERIMENTAL

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; Drug: hydroxychloroquine; Drug: paclitaxel

Interventions

bevacizumab BIOLOGICAL

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

Hydroxychloroquine, Carboplatin, Paclitaxel, Bevacizumab

carboplatin DRUG

Carboplatin will be given at AUC = 6 by IV over 15-30 minutes on Day 1 immediately following paclitaxel

Hydroxychloroquine, Carboplatin, Paclitaxel; Hydroxychloroquine, Carboplatin, Paclitaxel, Bevacizumab

hydroxychloroquine DRUG

200 mg orally BID (total daily dose of 400 mg)

Hydroxychloroquine, Carboplatin, Paclitaxel; Hydroxychloroquine, Carboplatin, Paclitaxel, Bevacizumab

paclitaxel DRUG

Dose of 200 mg/m2 IV on day 1 of each cycle

Hydroxychloroquine, Carboplatin, Paclitaxel; Hydroxychloroquine, Carboplatin, Paclitaxel, Bevacizumab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Medicine and Dentistry of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Cancer Institute of New Jersey at Hamilton

Hamilton, New Jersey, 08690, United States

Location

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

New Brunswick, New Jersey, 08903, United States

Location

Related Links

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

MeSH Terms

Conditions

Lung Neoplasms; Adenocarcinoma of Lung; Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; Carboplatin; Hydroxychloroquine; Paclitaxel

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. Joseph Aisner
• Organization: Cancer Institute of New Jersey

aisnerjo@cinj.rutgers.edu; rizzoji@cinj.rutgers.edu; zelinsta@cinj.rutgers.edu

732-235-8675

Study Officials

• Joseph Aisner, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2008
• First Posted: August 6, 2008
• Study Start: June 16, 2008
• Primary Completion: December 21, 2010
• Study Completion: December 21, 2010
• Last Updated: May 23, 2017
• Results First Posted: November 25, 2013

Record last verified: 2017-04

Locations

US (2)