Modulation of Autophagy in Patients With Advanced/Recurrent Non-small Cell Lung Cancer - Phase II

NCT01649947 | Completed Phase 2 Results

• 4 other identifiers: 0220110249P30CA072720NCI-2011-03731031105
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

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. Some patients who have a specific type of lung cancer can also receive another drug, a drug that targets blood vessels, called bevacizumab (also known as avastin). Hydroxychloroquine is an FDA approved drug for the treatment of malaria, rheumatoid arthritis and lupus erythematosis.

Conditions

Non-small Cell Lung Cancer; Advanced Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer

Keywords

Lung cancer; Non-small cell lung cancer; Advanced non-small cell lung cancer; Recurrent non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Antitumor Activity, as Measured by Tumor Response Rate of Hydroxychloroquine, Paclitaxel, Carboplatin, and Bevacizumab (for Eligible Patients) in Patients With Advanced or Recurrent NSCLC Cancer

  Assessed using RECIST criteria. Determined using a Simon's two-stage minimax design with a 5% significance level and 80% power.

  6 years

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  6 years

Study Arms (2)

Cohort 2: Bevacizumab ineligible patients

EXPERIMENTAL

Paclitaxel 200mg/m2 IV over 3 hours Carboplatin AUC= 6 IV over 15-30 min Hydroxychloroquine 200 mg PO BID

Drug: Paclitaxel; Drug: Carboplatin; Drug: Hydroxychloroquine

Cohort 1: Bevacizumab eligible patients

EXPERIMENTAL

Paclitaxel 200mg/m2 IV over 3 hours Carboplatin AUC= 6 IV over 15-30 min Bevacizumab 15 mg/kg IV over 90 min for Hydroxychloroquine 200 mg PO BID

Drug: Paclitaxel; Drug: Carboplatin; Drug: Hydroxychloroquine; Drug: Bevacizumab

Interventions

Paclitaxel DRUG

Paclitaxel will be given at a dose of 200 mg/m2(by IV over 3 hours on Day 1). Cycles every 3 weeks for 4-6 Cycles. Prior to receiving paclitaxel, all patients will receive the following premedication: * Dexamethasone 20 mg po 12 and 6 hours prior to paclitaxel infusion (patients may be treated with dexamethasone 20 mg iv \< 1 hour prior to infusion with paclitaxel if the patient did not take the oral dexamethasone) * Diphenydramine 50 mg iv (or equivalent) \< 1 hour prior to paclitaxel infusion * Ranitidine 50 mg iv \< 1 hour prior to paclitaxel infusion (alternatively other H2-blockers may be used)

Also known as: Taxol

Cohort 1: Bevacizumab eligible patients; Cohort 2: Bevacizumab ineligible patients

Carboplatin DRUG

Carboplatin will be given at AUC = 6 by IV over 15-30 minutes on Day 1 immediately following paclitaxel. Cycles every 3 weeks for 4-6 Cycles.

Also known as: Paraplatin

Cohort 1: Bevacizumab eligible patients; Cohort 2: Bevacizumab ineligible patients

Hydroxychloroquine DRUG

Hydroxychloroquine will be given as a flat dose of 200 mg orally BID (total daily dose of 400 mg). Cycles every 3 weeks for 4-6 Cycles.

Also known as: Plaquenil

Cohort 1: Bevacizumab eligible patients; Cohort 2: Bevacizumab ineligible patients

Bevacizumab DRUG

Cohort 1 only: Bevacizumab will be given by IV on Day 1 of each 21-day cycle at a dose of 15 mg/kg. Cycles every 3 weeks for 4-6 Cycles.

Also known as: Avastin

Cohort 1: Bevacizumab eligible patients

Eligibility Criteria

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

You may qualify if:

• Signed a protocol-specific informed consent.
• years of age or older.
• ECOG Performance Status 0 or 1.
• Cancer criteria:
• Histologically or cytologically confirmed non-small cell lung cancer. 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 IVa ((malignant pleural effusion (is now staged as stage IVa by the most recent staging system), or stage IV, or recurrent disease)).
• Measurable disease according to RECIST criteria.
• Patient with CNS metastasis are required to have stable disease documented by being off treatment (surgery, or Whole Brain radiation therapy) for at least 2 weeks, and four (4) weeks is preferred. No delay in onset of therapy is required for those patients who undergo stereotactic RT to the brain lesion(s). A contrast enhanced brain CT or brain MRI is required within 35 days of enrollment. Patients with brain metastases who qualify for protocol therapy will be included in Cohort 2 (ineligible for treatment with Bevacizumab).
• Prior radiation to sites other than the brain is allowed, if completed at least 2 weeks before treatment and provided that all radiation-related toxicities have resolved to ≤ Grade 1. Stereotactic irradiation to any site excludes the need for a waiting period.
• Laboratory requirements
• \- Adequate organ function, as evidenced by ALL the following:
• absolute neutrophil count (ANC) ≥ 1500/mm³
• platelet count ≥ 100,000/mm³
• hemoglobin ≥ 9 gm/dL
• total bilirubin ≤ 1.5 x ULN; if patient has Gilbert's disease, then patient must have isolated hyperbilirubinemia (e.g. no other liver function test abnormality), with maximum bilirubin ≤ 2 X institutional ULN.

You may not qualify if:

• Cancer criteria:
• 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.
• 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.
• Comorbidities
• For Cohort 1: (Bevacizumab eligible)
• 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 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 not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2.
• No history of significant vascular disease (eg aortic aneurysm).
• No current or recent (within 28 days of enrollment) full dose anticoagulants or thrombolytic agents.
• For Cohort 2 (Bevacizumab ineligible):
• None of the following conditions within 6 months prior to enrollment: myocardial infarction, stroke or symptomatic peripheral vascular disease.
• Patients must not have unstable angina or NYHA classification of congestive heart failure of Grade ≥ 2.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator
• Rutgers Cancer Institute of New Jersey: collaborator

Study Sites (2)

Robert Wood Johnson University Hospital at Hamilton

Hamilton, New Jersey, 08690, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Paclitaxel; Carboplatin; Hydroxychloroquine; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Joseph Aisner, MD
• Organization: Rutgers Cancer Institute of New Jersey

aisnerjo@cinj.rutgers.edu

732-235-7401

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2012
• First Posted: July 25, 2012
• Study Start: December 23, 2011
• Primary Completion: June 30, 2015
• Study Completion: June 30, 2015
• Last Updated: November 21, 2022
• Results First Posted: May 8, 2019

Record last verified: 2022-10

Locations

US (2)