Hydroxychloroquine With or Without Erlotinib in Advanced Non-small Cell Lung Cancer (NSCLC)

NCT01026844 | Terminated Phase 1 Results DMC

• 2 other identifiers: 07-037OSI4251s
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Erlotinib is a type of drug called a tyrosine kinase inhibitor (TKI). TKIs block a protein called epidermal growth factor receptor (EGFR). EGFR may control tumor growth and tumor cell survival. EGFR is found on the surface of many types of cancer cells, including non-small cell lung cancer (NSCLC). Erlotinib is approved by the Food and Drug Administration (FDA) for the treatment of NSCLC. Hydroxychloroquine (HCQ) is a drug approved by the FDA for treatment of malaria, rheumatoid arthritis, and several other diseases but is not currently thought of as a cancer treatment. Previous laboratory studies suggests that HCQ may have an anti-cancer effect by itself in some situations, particularly when EGFR TKI drugs have been useful in the past against the tumor. The two drugs together may be able to fight lung cancer in cases where erlotinib is no longer effective by itself. The purpose of this research study is to determine the highest dose of HCQ that can be given safely in combination with erlotinib. We will also begin to look at whether HCQ plus erlotinib helps treat cancer that have become resistant to TKI treatment after initially responding.

Conditions

Non-small Cell Lung Cancer

Keywords

erlotinib; tarceva; hydroxychloroquine; NSCLC

Outcome Measures

Primary Outcomes (1)

• Describe the Number and Type of Observed Dose Limiting Toxcities

  HCQ doses tested included 400mg, 600mg, 800mg, and 1000mg. Dose-limiting toxicities (DLTs) were defined as CTC of grade 2 or higher retinopathy or keratitis, or CTC of grade 3 or higher hematologic, skin, CNS, neuropathic, cardiac, respiratory, gastrointestinal, or renal AEs in the first cycle considered at least possibly related to HCQ. If a DLT was observed, an additional three patients were enrolled at that dose level. The maximum tolerated dose for HCQ in each arm would be defined as one dose level below that at which two or more of 6 patients experienced a DLT, or if no DLTs were observed, the highest tested dose.

  2 years

Secondary Outcomes (3)

• Determine the Pharmacokinetic (PK) Parameters of Hydroxychloroquine (HCQ) Plus Erlotinib.

  2 years

• Objective Tumor Response Rate

  2 years

• Correlate Epidermal Growth Factor Receptor (EGFR) Mutations and EGFR Amplification With Response to Treatment in Patients With Available Tumor Specimens.

  2 years

Study Arms (2)

Erlotinib plus hydroxychloroquine

EXPERIMENTAL

erltoinib 150mg per day plus HCQ in esclating doses of 400mg, 600mg, 800mg and 1000mg per day

Drug: erlotinib; Drug: hydroxychloroquine

Hydroxychloroqine

EXPERIMENTAL

hydroxychloroquine given at escalating doses of 400mg, 600mg, 800mg and 1000mg per day

Drug: hydroxychloroquine

Interventions

erlotinib DRUG

Taken orally once a day

Also known as: Tarceva

Erlotinib plus hydroxychloroquine

hydroxychloroquine DRUG

Taken orally once a day

Also known as: HCQ

Erlotinib plus hydroxychloroquine; Hydroxychloroqine

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed diagnosis of non-small cell lung cancer
• Stage IIIB with pleural effusion or Stage IV disease by the American Joint Committee on Cancer (AJCC) 6th edition staging criteria.
• At least 12 weeks of prior treatment with erlotinib, gefitinib, or another EGFR small molecule TKI agent.
• Age equal to or greater than 18 years
• Measurable disease, defined according to RECIST criteria
• Performance status of 0, 1 or 2
• At least 2 weeks since prior radiation treatment
• At least 2 weeks since any prior chemotherapy or targeted therapy
• Adequate organ function as outlined in the protocol
• Approval for HCQ treatment by an eye doctor, based on a screening eye exam. Examples of disqualifying baseline conditions include macular degeneration and other retinal disease.
• Willingness to comply with protocol procedures including the blood-sampling schedule for PK analyses and periodic eye examination

You may not qualify if:

• Current use of hydroxychloroquine for any reason
• Known hypersensitivity to chloroquine, hydroxychloroquine, or any other closely related drug
• Known hypersensitivity to erlotinib, gefitinib, or any closely related drug
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency, as HCQ may cause hemolytic anemia in patients with G6PD deficiency
• Cataracts that would interfere with required funduscopic examinations, or severe baseline visual impairment including macular degeneration, retinopathy or visual field changes, or having only one functional eye. All patients must undergo a screening eye exam prior to enrollment
• Pregnancy or breastfeeding. Female subjects of childbearing age and male subjects must practice acceptable method of birth control
• Symptomatic CNS metastases or newly diagnosed CNS metastases that have not yet been definitively treated with radiation and/or surgery
• Prior radiation therapy inclusive of all identified target lesions
• Any evidence of clinically active interstitial lung disease
• Malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
• Use of any non-FDA approved or investigational agent within 2 weeks of enrolling onto the trial, or failure to recover from the side effects of any of these agents
• Penicillamine use for Wilson's disease or any other indication, as concomitant use with HCQ can increase toxicity to penicillamine

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Goldberg SB, Supko JG, Neal JW, Muzikansky A, Digumarthy S, Fidias P, Temel JS, Heist RS, Shaw AT, McCarthy PO, Lynch TJ, Sharma S, Settleman JE, Sequist LV. A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer. J Thorac Oncol. 2012 Oct;7(10):1602-8. doi: 10.1097/JTO.0b013e318262de4a.

  PMID: 22878749 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Hydroxychloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chloroquine; Aminoquinolines; Quinolines

Limitations and Caveats

Early termination of study leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Lecia Sequist, MD
• Organization: Massachusetts General Hospital

lvsequist@partners.org

617-724-4000

Study Officials

• Lecia Sequist, MD, MPH

  Massachussets General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: December 2, 2009
• First Posted: December 4, 2009
• Study Start: July 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: January 30, 2017
• Results First Posted: July 31, 2013

Record last verified: 2017-01

Locations

US (1)