A Study of First-line Maintenance Erlotinib Versus Erlotinib at Disease Progression in Participants With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Platinum-Based Chemotherapy

NCT01328951 | Completed Phase 3 Results

• 1 other identifier: BO25460
• Study Type: interventional
• Target: 643
• Locations: 20 countries
• Sites: 155

Brief Summary

This double-blind, placebo-controlled study will evaluate the benefit of first-line maintenance erlotinib (Tarceva) versus erlotinib at the time of disease progression in participants with advanced NSCLC who have not progressed following 4 cycles of platinum based-chemotherapy and whose tumor does not harbor an epidermal growth factor receptor (EGFR)-activating mutation. Participants will be randomized to receive either erlotinib 150 milligrams (mg) orally (PO) once daily or placebo. Participants who progress on placebo will receive erlotinib 150 mg PO once daily as second-line therapy, and those who progress on erlotinib may switch to a non-investigational, second-line chemotherapy. Treatments will continue until disease progression, death, or unacceptable toxicity. Participants may also be entered into a final Survival Follow-Up (SFU) period upon treatment discontinuation.

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Who Died During the Overall Study

  Participants were followed for survival until death or premature withdrawal. The percentage of participants who died during the Overall Study (BP, OLP, or SFU) was calculated.

  Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death)

• Overall Survival (OS) as Median Time to Event During the Overall Study

  Participants were followed for survival until death or premature withdrawal. OS was defined as the interval between date of randomization and date of death from any cause. Median time to event during the Overall Study (BP, OLP, or SFU) was estimated using the Kaplan-Meier method and expressed in months.

  Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death)

• Percentage of Participants Event-Free (Alive) at 1 Year During the Overall Study

  Participants were followed for survival until death or premature withdrawal. The percentage of participants event-free (i.e., still alive) at 1 year during the Overall Study was calculated.

  At 1 year

Secondary Outcomes (6)

• Percentage of Participants Who Died or Experienced Disease Progression During Blinded Treatment

  Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

• Progression-Free Survival (PFS) as Median Time to Event During Blinded Treatment

  Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

• Percentage of Participants Event-Free (Alive and No Disease Progression) at 6 Months During Blinded Treatment

  At 6 months

• Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to RECIST During Blinded Treatment

  Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

• Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment

  Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

Study Arms (2)

Early Erlotinib

EXPERIMENTAL

Participants will receive blinded erlotinib as 150 mg PO once daily in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrate disease progression may be unblinded to receive an approved second-line therapy (but not EGFR targeted therapies) until disease progression, death, or unacceptable toxicity. Participants may be observed during a final SFU period after discontinuation from study treatment.

Drug: Erlotinib; Drug: Second-Line Chemotherapy

Late Erlotinib

PLACEBO COMPARATOR

Participants will receive blinded placebo tablets PO once daily in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrate disease progression may be unblinded to receive second-line erlotinib as 150 mg PO once daily until disease progression, death, or unacceptable toxicity. Participants may be observed during a final SFU period after discontinuation from study treatment.

Drug: Placebo; Drug: Erlotinib

Interventions

Placebo DRUG

Placebo will be administered PO once daily as first-line maintenance until disease progression, death, or unacceptable toxicity.

Late Erlotinib

Erlotinib DRUG

Erlotinib will be administered as 150 mg PO once daily until disease progression, death, or unacceptable toxicity, as first-line maintenance or as second-line therapy for those who progress while receiving placebo.

Also known as: Tarceva

Early Erlotinib; Late Erlotinib

Second-Line Chemotherapy DRUG

Participants who progress on first-line maintenance erlotinib may receive an approved second-line therapy (but not EGFR targeted therapies) until disease progression, death, or unacceptable toxicity. The selected chemotherapy will be non-investigational and chosen at the discretion of the Investigator.

Early Erlotinib

Eligibility Criteria

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

You may qualify if:

• Adults greater than or equal to (≥) 18 years of age, or legal age of consent if greater than 18
• Advanced or recurrent (Stage IIIB) or metastatic (Stage IV) NSCLC
• Completion of 4 cycles of platinum-based chemotherapy without progression (end of last chemotherapy cycle less than or equal to \[≤\] 28 days prior to randomization)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

You may not qualify if:

• Prior exposure to agents directed at human epidermal growth factor receptor (HER) axis (e.g. erlotinib, gefitinib, cetuximab)
• Participants whose tumors harbor an EGFR-activating mutation
• Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease before Screening
• Use of pemetrexed in maintenance setting (pemetrexed allowed during the chemotherapy run-in)
• Participants who have undergone complete tumor resection after responding to the platinum-based chemotherapy during the Screening phase
• Any other malignancies within 5 years, except for curatively resected carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ, or organ-confined prostate cancer
• Central nervous system (CNS) metastases or spinal cord compression that has not been definitely treated with surgery and/or radiation, or treated CNS metastases or spinal cord compression without stable disease for ≥2 months
• Human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
• Any inflammatory changes of the surface of the eye

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (155)

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Gilroy, California, 95020, United States

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Washington D.C., District of Columbia, 20010, United States

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Kansas City, Missouri, 64132, United States

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Missoula, Montana, 59802, United States

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Lebanon, New Hampshire, 03756, United States

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Dayton, Ohio, 45420, United States

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Chattanooga, Tennessee, 37404, United States

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Spokane, Washington, 99218, United States

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Tacoma, Washington, 98405, United States

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Belo Horizonte, Minas Gerais, 30150-281, Brazil

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Lajeado, Rio Grande do Sul, 95900-000, Brazil

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Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

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Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

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

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Porto Alegre, Rio Grande do Sul, 90470340, Brazil

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Ijuí, Rondônia, 98700-000, Brazil

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Florianópolis, Santa Catarina, 88034-000, Brazil

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Santo André, São Paulo, 09060-650, Brazil

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Gabrovo, 5300, Bulgaria

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Haskovo, 6300, Bulgaria

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Plovdiv, 4004, Bulgaria

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Rousse, 7000, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1303, Bulgaria

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Sofia, 1527, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, 1756, Bulgaria

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Sofia, 1784, Bulgaria

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Varna, 9010, Bulgaria

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Windsor, Ontario, N8W 2X3, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Québec, Quebec, G1V 4G5, Canada

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Regina, Saskatchewan, S4T 7T1, Canada

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Beijing, 100142, China

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Beijing, 100730, China

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Changchun, 130012, China

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Fuzhou, 350014, China

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Guangzhou, 510515, China

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Guangzhou, China

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Harbin, 150081, China

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Shanghai, 200030, China

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Shanghai, 200433, China

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Shantou, 515041, China

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Shenyang, 110001, China

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Suzhou, 215004, China

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Tianjin, 300060, China

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Wuhan, 430071, China

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Xi'an, 710061, China

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České Budějovice, 370 87, Czechia

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Jindřichův Hradec, 377 01, Czechia

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Nymburk, 288 01, Czechia

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Ostrava - Poruba, 708 52, Czechia

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Prague, 150 06, Czechia

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Prague, 180 81, Czechia

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Tábor, 390 03, Czechia

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Bayonne, 64109, France

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Compiègne, 60321, France

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Gap, 05007, France

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Libourne, 33505, France

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Lille, 59020, France

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Nantes, 44202, France

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Saint-Brieuc, 22027, France

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Villefranche-sur-Saône, 69655, France

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Budapest, 1121, Hungary

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Budapest, 1122, Hungary

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Budapest, 1125, Hungary

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Budapest, 1145, Hungary

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Deszk, 6772, Hungary

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Farkasgyepű, 8582, Hungary

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Győr, 9024, Hungary

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Gyula, 5703, Hungary

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Mátraháza, 3233, Hungary

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Miskolc, 3526, Hungary

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Székesfehérvár, 8000, Hungary

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Szolnok, 5000, Hungary

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Törökbálint, 2045, Hungary

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Zalaegerszeg, 8900, Hungary

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S. Giovanni Rotondo, Apulia, 71013, Italy

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Avellino, Campania, 83100, Italy

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Bologna, Emilia-Romagna, 40138, Italy

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Parma, Emilia-Romagna, 43100, Italy

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Rome, Lazio, 00144, Italy

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Rome, Lazio, 00151, Italy

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Rome, Lazio, 00168, Italy

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Legnago, Lombardy, 37045, Italy

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Treviglio, Lombardy, 24047, Italy

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Livorno, Tuscany, 57124, Italy

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Pisa, Tuscany, 56100, Italy

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Verona, Veneto, 37134, Italy

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Daugavpils, 5417, Latvia

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Riga, LV-1079, Latvia

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Riga, LV1002, Latvia

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Kaunas, 50009, Lithuania

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Vilnius, 08660, Lithuania

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Arnhem, 6800 TA, Netherlands

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Heerlen, 6419 PC, Netherlands

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Hoorn, 1625 HV, Netherlands

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Sittard-Geleen, 6162 BG, Netherlands

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Zutphen, 7207 AE, Netherlands

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Brzozów, 36-200, Poland

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Krakow, 31-115, Poland

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Poznan, 60-569, Poland

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Wodzisław Śląski, 44-300, Poland

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Zamość, 22-400, Poland

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Baia Mare, 430031, Romania

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Brasov, 500091, Romania

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Brasov, 500152, Romania

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Brăila, 810325, Romania

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Bucharest, 010976, Romania

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Bucharest, 022328, Romania

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Cluj-Napoca, 400015, Romania

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Cluj-Napoca, 400058, Romania

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Cluj-Napoca, 400132, Romania

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Oradea, 410167, Romania

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Ploieşti, 100337, Romania

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Târgu Mureş, 540136, Romania

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Banská Bystrica, 975 17, Slovakia

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Bardejov, 085 01, Slovakia

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Košice, 04001, Slovakia

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Nové Zámky, 940 02, Slovakia

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Poprad, 058 01, Slovakia

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Rimavská Sobota, 97901, Slovakia

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Cape Town, 7570, South Africa

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Cape Town, 7700, South Africa

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George, 6530, South Africa

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Port Elizabeth, 6045, South Africa

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Pretoria, 0002, South Africa

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Gyeonggi-do, 463-707, South Korea

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Seoul, 03722, South Korea

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Seoul, 06351, South Korea

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Seoul, 150-713, South Korea

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Suwon, 442-723, South Korea

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Kaohsiung City, 00833, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 00112, Taiwan

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Taipei, 100, Taiwan

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Taipei, 112, Taiwan

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Taipei, 11490, Taiwan

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Bangkok, 10700, Thailand

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Hat Yai, 90110, Thailand

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Muang, 50200, Thailand

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Muang, 57000, Thailand

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Dnipropetrovsk, 49102, Ukraine

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Donetsk, 83092, Ukraine

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Kharkiv, 61024, Ukraine

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Kirovograd, 25011, Ukraine

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Kyiv, 03022, Ukraine

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Kyiv, 03115, Ukraine

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Kyiv, 04107, Ukraine

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Lutsk, 63000, Ukraine

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Sumy, 40005, Ukraine

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Uzhhorod, 88000, Ukraine

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Vinnytsia, 21029, Ukraine

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Zaporizhzhya, 69040, Ukraine

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MeSH Terms

Interventions

Erlotinib Hydrochloride

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Following the final analysis, the study was closed and all remaining participants were withdrawn from the study and considered "Not Completed" (as presented in the Participant Flow). However, the overall status of study was confirmed as completed.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2011
• First Posted: April 5, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: October 28, 2016
• Results First Posted: February 29, 2016

Record last verified: 2016-06

Locations

IT (12); ZA (5); CN (15); CZ (7); SL (6); UA (12); RO (12); TW (7); BR (9); BU (11); LA (3); TH (4); FR (8); US (9); PL (5); KR (5); HU (14); CA (4); NL (5); LI (2)