Hydroxychloroquine and Gefitinib to Treat Lung Cancer

NCT00809237 | Unknown Phase 1 DMC

• 2 other identifiers: NS 01/03/082008/00196
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality in men and women in Singapore.Chemotherapy and biologically targeted agents can extend survival only modestly for these patients; therefore, discovery of novel ways to prolong the disease course is a top research priority. The epidermal growth factor receptor (EGFR) signaling pathway plays a central role in the neoplastic transformation of NSCLC and promotes cancer cell survival, metastasis, and angiogenesis. The predominance of EGFR signaling in NSCLC makes the pathway an attractive candidate for the development of targeted therapeutics. Over the last three years, the FDA has approved two drugs for salvage treatment of NSCLC, gefitinib (Iressa ®, formerly known as ZD1839) and erlotinib (Tarceva ®, formerly known as OSI-774). Both are small molecule orally-bioavailable tyrosine kinase inhibitors (TKIs) of the EGFR TK domain, and have been shown to improve survival compared to placebo in asian patients when administered after failure of first or second line chemotherapy for advanced NSCLC.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer; Gefitinib; Hydroxychloroquine

Outcome Measures

Primary Outcomes (2)

• For the phase I lead in study: To identify the tolerability, the dose limiting toxicity (DLT) and the general safety profile of HCQ and gefitinib when used in combination.

  2 years

• For the phase II study: To determine the response rates to HCQ and Gefitinib.

  2 years

Secondary Outcomes (2)

• For the phase I lead in study: To determine the PK (pharmacokinetic) parameters of HCQ plus gefitinib.

  2 years

• For the phase II study: To determine the time to progression for patients treated with HCQ and Gefitinib.

  2 years

Study Arms (1)

Gefitinib, Hydroxychloroquine

EXPERIMENTAL

For the lead in phase I study, recruited patients will receive one week of 250 mg of Gefitinib, before HCQ at the assigned dose is introduced in addition to Gefitinib 250 mg om. After the MTD of HCQ is determined, the phase II study will proceed with the combination of 250 mg of Gefitinib and the MTD dose of HCQ.

Drug: Gefitinib, Hydroxychloroquine

Interventions

Gefitinib, Hydroxychloroquine DRUG

Gefitinib 250 mg om Hydroxychloroquine at maximally tolerated dose

Also known as: Iressa

Gefitinib, Hydroxychloroquine

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For the lead in phase I study:
• 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.
• Age equal to or greater than 21 years
• Measurable disease, defined according to RECIST criteria
• Performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group(ECOG) Performance Status scale.
• At least 2 weeks since prior radiation treatment, chemotherapy or targeted therapy (from the day that protocol treatment begins).
• Patients who had been on gefitinib should have a wash out period of two weeks prior to commencement of treatment drugs for this study.
• Adequate organ function including the following:
• Adequate bone marrow reserve:
• Total white blood cell count (WBC) \> 3.0 x 109/L
• Platelet count \>100 x 109/L
• Hemoglobin \>8 g/dL
• Hepatic:
• Bilirubin: = 1.25 times the upper limit of normal (ULN)

You may not qualify if:

• Willingness to comply with protocol procedures including the blood-sampling schedule for PK analyses and periodic eye examinations.
• Willingness to participate in clinical research as evidenced by their signature on the informed consent form.
• Tumor block from subject's biopsy or surgical resection specimen should ideally be available but is not a mandatory requirement for study entry.
• For the phase II study:
• NSCLC patients must be non-smokers and have adenocarcinomas.
• Patients who had been on gefitinib should have a wash out period of two weeks prior to commencement of treatment drugs for this study. They must have responded to Gefitinib previously (either CR, PR or SD) for more than twelve weeks to be eligible.
• For both lead in phase I and phase II study:
• Current use of hydroxychloroquine for any reason.
• Known hypersensitivity to chloroquine, hydroxychloroquine, or any 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.
• Pregnant or breastfeeding. HCQ crosses the placenta and use is not recommended during pregnancy except for life-threatening malaria. The effects of gefitinib on a fetus are unknown. For these reasons, female subjects of childbearing age must practice acceptable methods of birth control to avoid pregnancy. Male subjects must also practice acceptable methods of birth control to prevent pregnancy of a partner.
• Symptomatic CNS metastases or newly diagnosed CNS metastases that have not yet been definitively treated with radiation and/or surgery. Note that patients with a history of CNS metastases or cord compression are allowable if they have been definitively treated and are clinically stable. Maintenance steroids are allowed but maintenance seizure medication is not allowed.
• Prior radiation therapy inclusive of all identified target lesions. Note that prior palliative radiation to bony disease, CNS disease, or a limited thoracic area is allowed, provided that there is measurable disease outside the field and radiation is completed at least two weeks prior to starting treatment and the patient has fully recovered from all side effects.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Massachusetts General Hospital: collaborator
• AstraZeneca: collaborator

Study Sites (1)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib; 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

Study Officials

• Tan Min Chin, MD

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tan Min Chin, MD

CONTACT

65-67724140; Tan_Min_CHIN@nuhs.com.sg

Boon Cher Goh, MD

CONTACT

65-67724140; Boon_Cher_GOH@nuhs.com.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Chin Tan Min

Study Record Dates

• First Submitted: December 16, 2008
• First Posted: December 17, 2008
• Study Start: November 1, 2008
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

SG (1)