Study of Pralatrexate vs. Erlotinib for Non-Small Cell Lung Cancer After at Least 1 Prior Platinum-based Treatment

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Randomized, Phase 2b, Multi-center Study of Pralatrexate Versus Erlotinib in Patients With Stage IIIB/IV Non-small Cell Lung Cancer After Failure of at Least 1 Prior Platinum-based Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00606502
• Other study ID #: PDX-012
• Secondary ID: 2007-004673-26
• Status: Completed
• Phase: Phase 2
• Start date: January 2008
• Est. completion date: June 24, 2010

Study information

• Verified date: February 2021
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical study is to determine the effectiveness (ability to provide beneficial treatment of the disease) and safety of pralatrexate compared to erlotinib when given to non-small cell lung cancer (NSCLC) patients who are current or former cigarette smokers and who have received at least 1 prior treatment with a platinum drug (cisplatin or carboplatin)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: June 24, 2010
• Est. primary completion date: June 24, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed Stage IIIB/ IV non-small cell lung cancer (NSCLC).
• Relapsed after treatment with 1 or 2 prior chemotherapy regimens, including at least 1 platinum-based treatment. Patients may have received pemetrexed as 1 of the prior therapies. Patients may not have received investigational therapy as their only prior therapy.
• Recovered from the toxic effects of prior therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Smoked = 100 cigarettes in their lifetime, whether a former or current cigarette smoker.
• Adequate blood, liver and kidney function as defined by laboratory values.
• Received 1-1.25 mg daily oral folic acid for at least 7 days prior to randomization and 1 mg intramuscular injection of vitamin B12 within 10 weeks prior to randomization.
• Women of childbearing potential must use medically acceptable birth control and have a negative serum pregnancy test within 14 days prior to randomization. Patients who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized do not require this test.
• Men who are not surgically sterile must use medically safe and effective birth control from the time of study randomization, and agree to continue practicing until at least 90 days after the last administration of study treatment.
• Accessible for repeat dosing and follow-up.
• Give written informed consent.

Exclusion Criteria:

• Active concurrent primary malignancy (except non-melanoma skin cancer or in situ carcinoma of the cervix). If there is a history of prior malignancy, the patient must be disease-free for = 5 years. Patients with other prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no evidence of active or recurrent disease.
• Use of investigational drugs, biologics, or devices within 4 weeks prior to randomization.
• Previous exposure to pralatrexate or erlotinib.
• Women who are pregnant or breastfeeding.
• Congestive Heart Failure Class III/IV according to New York Heart Association (NYHA) Functional Classification.
• Uncontrolled hypertension.
• Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of <100 mm3 or detectable viral load within the past 3 months, and is receiving combination anti-retroviral therapy.
• Symptomatic central nervous system metastases or lesions for which treatment is required.
• Major surgery within 2 weeks of study randomization.
• Receipt of any conventional systemic chemotherapy within 4 weeks (6 weeks for nitrosoureas, mitomycin C), or radiation therapy (RT) within 2 weeks, prior to randomization.
• Active infection or any serious underlying medical condition, which would impair the ability of the patient to receive protocol treatment.
• Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent or limit study compliance.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Pralatrexate
Intravenous (IV) push administration over 3-5 minutes into a patent IV line containing normal saline (0.9% sodium chloride). Initial dose: 230 mg/m2, increased to 270 mg/m2 if patient does not have specific adverse events (AEs) as per the protocol after receipt of 2 consecutive doses 2 weeks apart. Reductions allowed in 40 mg/m2 decrements to 190 mg/m2 per the protocol defined dose modifications. Protocol amended dose: 190 mg/m2, then 230 mg/m2 if patient does not have specific AEs per the protocol after receipt of 2 consecutive doses 2 weeks apart. Reductions allowed in 40 mg/2 decrements to 150 mg/m2 per the protocol defined dose modifications. Administered on days 1 and 15 of a 4-week cycle (every 2 weeks) until criteria for discontinuation per the protocol are met.
• Erlotinib
150 mg orally in tablet form Administered daily 1 hour before or 2 hours after ingestion of food until criteria for discontinuation per the protocol are met.

Dietary Supplement:
• Vitamin B12
1 mg intramuscular injection Administered within 10 weeks of randomization, every 8-10 weeks throughout the study and for at least 30 days after last dose of study treatment.
• Folic Acid
1-1.25 mg orally Administered daily for at least 7 days prior to randomization, throughout the study and for at least 30 days after last dose of study treatment.

Locations

Country	Name	City	State
Argentina	Policlinica Privada - Instituto de Medicina Nuclear	Bahia Blanca	Provincia De Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming	Buenos Aires	Cuidad De Buenos Aires
Argentina	Hospital Britanico	Capital Federal
Argentina	Centro Oncologico Rosario	Rosario
Argentina	ISIS Clinica Especializada	Santa Fe
Argentina	CAIPO (Centero Para la Atencion Integral del Paciente Oncologico)	Tucuman
Brazil	Fundação Pio XII - Hospital do Câncer de Barretos	Barretos	SP
Brazil	Biocancer S.A.	Belo Horizonte
Brazil	Associação Hospital de Caridade de Ijuí	Ijui	RS
Brazil	Clinionco - Clínica de Oncologia de Porto Alegre	Porto Alegre	RS
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS
Brazil	Instituto do Cancer - Arnaldo Vieira de Carvalho	Sao Paulo
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Palacký University Medical School and Teaching Hospital	Olomouc
Czechia	Vitkovicka nemocnice, a. s.	Ostrava
Czechia	Fakultni nemocnice v Motole	Praha
Czechia	Nemocnice Na Homolce	Praha
Czechia	Fakultni nemocnice na Bulovce	Praha 8
Hungary	National Koranyi TBC and Pulmonology Institute	Budapest	Pest
Hungary	Matrai Allami Gyogyintezet	Matrahaza
Hungary	Jósa András Teaching Hospital	Nyiregyhaza	Szabolcs-Szatmár-Bereg
Hungary	Vas County Markusovszky Hospital	Szombathely	Vas
Hungary	Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza	Tatabánya
Hungary	Zala County Hospital	Zalaegerszeg	Zala
India	Kidwai Memorial Institute of Oncology	Bangalore	Karnataka
India	MNJ Radium Hospital and Radium Institute of Oncology and Regional Cancer Centre	Hyderabaad	Andhra Pradesh
India	Indo American Cancer Institute and Research Center	Hyderabad	Andhra Pradesh
India	B.P. Poddar Cancer Institute	Kolkata	West Bengal
India	Tata Memorial Hospital	Mumbai	Maharashtra
India	Dharmashila Cancer Hospital & Research Centre	New Delhi
India	Jehangir Clinical Development Centre Pvt Ltd	Pune	Mahara
India	Regional Cancer Center	Trivandrum	Kerala
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Summit Medical Group	Berkeley Heights	New Jersey
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Providence Everett Medical Center	Everett	Washington
United States	Donald Berdeaux	Great Falls	Montana
United States	Baptist Regional Cancer Center	Knoxville	Tennessee
United States	New York Oncology Hematology-Oncology Associates, P.C.	Latham	New York
United States	Signal Point Clinical Research Center	Middletown	Ohio
United States	Hematology and Oncology Associates South Jersey	Mount Holly	New Jersey
United States	New Bern Cancer Care	New Bern	North Carolina
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Cancer Therapy and Research Center	San Antonio	Texas
United States	Sharp Memorial Hospital	San Diego	California
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Czechia,  Hungary,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) of Patients Receiving Pralatrexate vs. Erlotinib	OS was defined as the length of time from randomization until death due to any cause. Patients who were alive at the time of the data cut-off date were censored at the last contact date.	Assessed from date of randomization no less frequently than every 16 weeks for up to 2 years after randomization.
Secondary	Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib	Number of patients whose tumors responded to Pralatrexate or Erlotinib, using the Response Criteria in Solid Tumors (RECIST).	Assessed every 8 weeks for the first 24 weeks, then every 16 weeks for up to 2 years or until PD or start of subsequent treatment.
Secondary	Progression-free Survival (PFS) of Patients Receiving Pralatrexate vs. Erlotinib	PFS was calculated as the number of days from randomization to the date of radiological evidence of PD or death due to any cause.	Assessed every 8 weeks for the first 24 weeks, then every 16 weeks for up to 2 years or until PD or start of subsequent treatment.
Secondary	Adverse Events of Patients Receiving Pralatrexate vs. Erlotinib		Assessed every 2 weeks while on treatment through safety follow-up visit (35 +/-5 days post-last dose) or early termination visit (at time of withdrawal).