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

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

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)

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pralatrexate; Dietary supplement: Vitamin B12; Dietary supplement: Folic Acid; Drug: Erlotinib

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal, Argentina, C1280AEB
    • Hospital Británico
  • Rosario, Argentina, S2000DSK
    • Centro Oncologico Rosario
  • Santa Fe, Argentina, S3000FFU
    • ISIS Clinica Especializada
  • Tucuman, Argentina, 4000
    • CAIPO (Centero Para la Atencion Integral del Paciente Oncologico)
  • Cuidad De Buenos Aires
    • Buenos Aires, Cuidad De Buenos Aires, Argentina, C1426ANZ
      • Instituto Médico Especializado Alexander Fleming
  • Provincia De Buenos Aires
    • Bahia Blanca, Provincia De Buenos Aires, Argentina, B8000FJI
      • Policlinica Privada - Instituto de Medicina Nuclear
• Brazil
  • Belo Horizonte, Brazil, 30150-270
    • Biocancer S.A.
  • Sao Paulo, Brazil, 01224-010
    • Instituto do Cancer - Arnaldo Vieira de Carvalho
  • RS
    • Ijui, RS, Brazil, 98700-000
      • Associacao Hospital de Caridade de Ijui
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
    • Porto Alegre, RS, Brazil, 90430-090
      • Clinionco - Clínica de Oncologia de Porto Alegre
  • SP
    • Barretos, SP, Brazil, 14780-400
      • Fundacao Pio XII - Hospital do Cancer de Barretos
• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv onkologicky ustav
  • Olomouc, Czechia, 775 20
    • Palacký University Medical School and Teaching Hospital
  • Ostrava, Czechia, 703 84
    • Vitkovicka nemocnice, a. s.
  • Praha, Czechia, 150 06
    • Fakultní nemocnice v Motole
  • Praha, Czechia, 15003
    • Nemocnice Na Homolce
  • Praha 8, Czechia, 180 00
    • Fakultni nemocnice Na Bulovce
• Hungary
  • Matrahaza, Hungary, 3233
    • Matrai Allami Gyogyintezet
  • Tatabánya, Hungary, 2800
    • Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza
  • Pest
    • Budapest, Pest, Hungary, 1525
      • National Koranyi TBC and Pulmonology Institute
  • Szabolcs-Szatmár-Bereg
    • Nyiregyhaza, Szabolcs-Szatmár-Bereg, Hungary, 4412
      • Josa Andras Teaching Hospital
  • Vas
    • Szombathely, Vas, Hungary, 9700
      • Vas County Markusovszky Hospital
  • Zala
    • Zalaegerszeg, Zala, Hungary, 8900
      • Zala County Hospital
• India
  • New Delhi, India, 110096
    • Dharmashila Cancer Hospital & Research Centre
  • Andhra Pradesh
    • Hyderabaad, Andhra Pradesh, India, 500004
      • MNJ Radium Hospital and Radium Institute of Oncology and Regional Cancer Centre
    • Hyderabad, Andhra Pradesh, India, 500034
      • Indo American Cancer Institute and Research Center
  • Karnataka
    • Bangalore, Karnataka, India, 560029
      • Kidwai Memorial Institute of Oncology
  • Kerala
    • Trivandrum, Kerala, India, 695011
      • Regional Cancer Center
  • Mahara
    • Pune, Mahara, India, 411001
      • Jehangir Clinical Development Centre Pvt Ltd
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Tata Memorial Hospital
  • West Bengal
    • Kolkata, West Bengal, India, 700053
      • B.P. Poddar Cancer Institute
• United States
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood And Cancer Center
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
  • Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Montana
    • Great Falls, Montana, United States, 59405
      • Donald Berdeaux
  • New Jersey
    • Berkeley Heights, New Jersey, United States, 07922
      • Summit Medical Group
    • Mount Holly, New Jersey, United States, 08060
      • Hematology and Oncology Associates South Jersey
  • New York
    • Latham, New York, United States, 12110
      • New York Oncology Hematology-Oncology Associates, P.C.
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • New Bern, North Carolina, United States, 28562
      • New Bern Cancer Care
  • Ohio
    • Middletown, Ohio, United States, 45042
      • Signal Point Clinical Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Baptist Regional Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Everett Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pralatrexate; Intravenous (IV) push administration over 3-5 minutes into a patent IV line containing normal saline (0.9% sodium chloride).	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.; Other Names: FOLOTYN; PDX; (RS)-10-propargyl-10-deazaaminopterin; 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.; Other Names: Cyanocobalamin; Dietary supplement: 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.; Other Names: Vitamin B9; Folate; Folacin
Active Comparator: 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.; Other Names: Cyanocobalamin; Dietary supplement: 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.; Other Names: Vitamin B9; Folate; Folacin; Drug: 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.; Other Names: Erlotinib hydrochloride; Tarceva®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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).

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 24, 2010
• Study Completion (Actual): June 24, 2010

Study Registration Dates

• First Submitted: January 22, 2008
• First Submitted That Met QC Criteria: February 1, 2008
• First Posted (Estimate): February 4, 2008

Study Record Updates

• Last Update Posted (Actual): March 5, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Lung Cancer; NSCLC; Smoking; Non-small cell lung cancer; PDX; Pralatrexate; Erlotinib; Tarceva; Smoker; Stage IIIB/IV non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Micronutrients; Protein Kinase Inhibitors; Hematinics; Folic Acid Antagonists; Erlotinib Hydrochloride; Vitamins; Folic Acid; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex; 10-deazaaminopterin
• Other Study ID Numbers: PDX-012; 2007-004673-26 (EudraCT Number)