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

NCT00606502 | Completed Phase 2 Results

• 2 other identifiers: PDX-0122007-004673-26
• Study Type: interventional
• Target: 201
• Locations: 6 countries
• Sites: 47

Brief 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)

Conditions

Non-small Cell Lung Cancer

Keywords

Stage IIIB/IV non-small cell lung cancer; Non-small cell lung cancer; NSCLC; Lung Cancer; Pralatrexate; Erlotinib; Tarceva; PDX; Smoking; Smoker

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Response Rate (RR) to Treatment of Patients Receiving Pralatrexate vs. Erlotinib

  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

  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).

Study Arms (2)

Pralatrexate

EXPERIMENTAL

Intravenous (IV) push administration over 3-5 minutes into a patent IV line containing normal saline (0.9% sodium chloride).

Drug: Pralatrexate; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid

Erlotinib

ACTIVE COMPARATOR

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.

Drug: Erlotinib; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid

Interventions

Pralatrexate DRUG

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.

Also known as: FOLOTYN, PDX, (RS)-10-propargyl-10-deazaaminopterin

Pralatrexate

Erlotinib DRUG

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.

Also known as: Tarceva®, Erlotinib hydrochloride

Erlotinib

Vitamin B12 DIETARY_SUPPLEMENT

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.

Also known as: Cyanocobalamin

Erlotinib; Pralatrexate

Folic Acid DIETARY_SUPPLEMENT

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.

Also known as: Vitamin B9, Folate, Folacin

Erlotinib; Pralatrexate

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead

Study Sites (47)

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Donald Berdeaux

Great Falls, Montana, 59405, United States

Location

Summit Medical Group

Berkeley Heights, New Jersey, 07922, United States

Location

Hematology and Oncology Associates South Jersey

Mount Holly, New Jersey, 08060, United States

Location

New York Oncology Hematology-Oncology Associates, P.C.

Latham, New York, 12110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

New Bern Cancer Care

New Bern, North Carolina, 28562, United States

Location

Signal Point Clinical Research Center

Middletown, Ohio, 45042, United States

Location

Baptist Regional Cancer Center

Knoxville, Tennessee, 37920, United States

Location

Cancer Therapy and Research Center

San Antonio, Texas, 78229, United States

Location

Providence Everett Medical Center

Everett, Washington, 98201, United States

Location

Policlinica Privada - Instituto de Medicina Nuclear

Bahía Blanca, Buenos Aires, B8000FJI, Argentina

Location

Instituto Medico Especializado Alexander Fleming

Buenos Aires, Cuidad de Buenos Aires, C1426ANZ, Argentina

Location

Hospital Britanico

Capital Federal, C1280AEB, Argentina

Location

Centro Oncologico Rosario

Rosario, S2000DSK, Argentina

Location

CAIPO (Centero Para la Atencion Integral del Paciente Oncologico)

San Miguel de Tucumán, 4000, Argentina

Location

ISIS Clinica Especializada

Santa Fe, S3000FFU, Argentina

Location

Associação Hospital de Caridade de Ijuí

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Clinionco - Clínica de Oncologia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90430-090, Brazil

Location

Fundação Pio XII - Hospital do Câncer de Barretos

Barretos, São Paulo, 14780-400, Brazil

Location

Biocancer S.A.

Belo Horizonte, 30150-270, Brazil

Location

Instituto do Cancer - Arnaldo Vieira de Carvalho

São Paulo, 01224-010, Brazil

Location

Masarykuv onkologicky ustav

Brno, 656 53, Czechia

Location

Palacký University Medical School and Teaching Hospital

Olomouc, 775 20, Czechia

Location

Vitkovicka nemocnice, a. s.

Ostrava, 703 84, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Nemocnice Na Homolce

Prague, 15003, Czechia

Location

Fakultni nemocnice na Bulovce

Prague, 180 00, Czechia

Location

National Koranyi TBC and Pulmonology Institute

Budapest, Pest County, 1525, Hungary

Location

Jósa András Teaching Hospital

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4412, Hungary

Location

Vas County Markusovszky Hospital

Szombathely, Vas County, 9700, Hungary

Location

Zala County Hospital

Zalaegerszeg, Zala County, 8900, Hungary

Location

Matrai Allami Gyogyintezet

Mátraháza, 3233, Hungary

Location

Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza

Tatabánya, 2800, Hungary

Location

MNJ Radium Hospital and Radium Institute of Oncology and Regional Cancer Centre

Hyderabaad, Andhra Pradesh, 500004, India

Location

Indo American Cancer Institute and Research Center

Hyderabad, Andhra Pradesh, 500034, India

Location

Kidwai Memorial Institute of Oncology

Bangalore, Karnataka, 560029, India

Location

Regional Cancer Center

Trivandrum, Kerala, 695011, India

Location

Tata Memorial Hospital

Mumbai, Maharashtra, 400012, India

Location

Jehangir Clinical Development Centre Pvt Ltd

Pune, Mahara, 411001, India

Location

B.P. Poddar Cancer Institute

Kolkata, West Bengal, 700053, India

Location

Dharmashila Cancer Hospital & Research Centre

New Delhi, 110096, India

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Smoking

Interventions

10-propargyl-10-deazaaminopterin; Erlotinib Hydrochloride; Vitamin B 12; Folic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds; Pterins; Pteridines

Limitations and Caveats

The date of the CRF database cut-off for patients (no further case report form or query data entry) was 24 Jun 2010. As of the CRF data cut-off date, 3 patients, remained on therapy.

Results Point of Contact

• Title: Medical Monitor
• Organization: Allos Therapeutics, Inc

gweems@allos.com

303-426-6262

Study Officials

• Garry Weems, PharmD

  Spectrum Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2008
• First Posted: February 4, 2008
• Study Start: January 1, 2008
• Primary Completion: June 24, 2010
• Study Completion: June 24, 2010
• Last Updated: March 5, 2021
• Results First Posted: January 20, 2011

Record last verified: 2021-02

Locations

HU (6); IN (8); US (15); BR (6); CZ (6); AR (6)