A Phase 2 Study Comparing TAS-102 Versus Topotecan or Amrubicin to Treat Small Cell Lung Cancer Following Platinum-Based Chemotherapy

An Open-Label, Randomized, Phase 2 Study Comparing TAS-102 Versus Topotecan or Amrubicin in Patients Requiring Second-Line Chemotherapy for Small Cell Lung Cancer That is Refractory or Sensitive to First-Line Platinum-Based Chemotherapy

The purpose of this trial is to compare the effects of TAS-102 with either amrubicin or topotecan (drugs used in Small Cell Lung Cancer) on lung cancer to find out the effects on survival, how much time may pass without disease progression, and the safety of TAS-102.

Study Overview

• Status: Terminated
• Conditions: Small Cell Lung Cancer (SCLC)
• Intervention / Treatment: Drug: TAS-102; Drug: Amrubicin (Japan); Drug: Topotecan (Japan/Europe)

Detailed Description

This is a multicenter, open-label, two-arm, randomized Phase 2 study of TAS-102 versus Investigator's choice of therapy in patients requiring second-line chemotherapy for SCLC refractory or sensitive to first-line platinum-based chemotherapy. Investigator's choice of therapy is defined as second-line chemotherapy with IV topotecan (Europe/Japan) or IV amrubicin (Japan). Patients will be stratified by response to first-line platinum-based chemotherapy (sensitive vs refractory). Sensitive patients are defined as patients who did not progress within 90 days after the last dose, and refractory patients are defined as patients who never responded or who responded but had radiologic progression < 90 days after the last dose.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Lungenklinik Heckeshorn- HELIOS Kliniken GmbH
  • Grosshansdorf, Germany
    • LungenClinic Grosshansdorf
  • Koplin, Germany
    • Klinikum Koeln-Merheim
  • Mainz, Germany
    • St. Hildegardis-Krankenhaus- Katholisches Klinikum Mainz
  • Muenchen, Germany
    • LMU-Campus Innenstadt
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany
      • Klinikum Mannheim GmbH Universitaetsklinikum
• Italy
  • Aviano, Italy
    • IRCCS Centro di Riferimento Oncologico di Aviano, Divisione Oncologia Medica A
  • Bari, Italy
    • Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
  • Catania, Italy
    • Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico
  • Cremona, Italy
    • Azienda Ospedaliera Instituti Ospitalieri di Cremona
  • Firenze, Italy
    • Azienda Ospedaliera Universitaria Careggi
  • Milano, Italy
    • IEO Istituto Europeo di Oncologia
  • Monza, Italy
    • Azienda Ospedaliera San Gerardo U.O Oncologia Medica
  • Reggio Emilia, Italy
    • Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
  • Sondalo, Italy
    • A.O.V.V. Ospedale Eugenio Morelli-Sondalo
  • Turin
    • Orbassano, Turin, Italy
      • Azienda Ospedaliero-Universitaria S. Luigi Gonzaga
• Japan
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
  • Fukuoka, Japan, 811-1395
    • National Kyushi Cancer Center
  • Hyogo, Japan, 673-8588
    • Hyogo Cancer Center
  • Saitama, Japan, 362-0806
    • Saitama Cancer Center
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Tokyo, Japan, 135-8550
    • Cancer Institute Hospital of Japanese Foundation for Cancer Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Has provided written informed consent
2. Is ≥18 years of age for patients enrolled in Europe; or ≥20 years of age for patients enrolled in Japan
3. Has definitive histologically or cytologically confirmed SCLC (limited or extensive disease)
4. Has progressed or had recurrence within 30 days prior to randomization
5. Has at least one measurable lesion, as defined by RECIST criteria version 1.1
6. ECOG performance status of 0, 1, or 2
7. Is able to take medications orally
8. Has adequate organ function (bone marrow, kidney and liver)
9. Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.

Exclusion Criteria:

1. Has cerebral metastases (unless metastases have been treated and controlled, metastases have been stable for at least 2-months post-intervention, and patient is not receiving corticosteroid treatment)
2. Certain serious illnesses or medical condition(s)
3. Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent, within the specified time frames prior to study drug administration
4. Has received TAS-102
5. Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies
6. Is a pregnant or lactating female

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: TAS-102	Drug: TAS-102; 35 mg/m2/dose, orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.
Active Comparator: Investigator Choice of Amrubicin or Topotecan; Investigator Choice of Amrubicin (Japan only) or Topotecan (Europe and Japan)	Drug: Amrubicin (Japan); Patients will receive treatment administered according to the country-specific approved prescribing information; Other Names: Calsed; Drug: Topotecan (Japan/Europe); Patients will receive treatment administered according to the country-specific approved prescribing information; Other Names: Hycamtin; Hycamptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Tumor assessments will be performed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 every 6 weeks during study treatment, and every 8 weeks after treatment is completed. Tumor assessments will be performed from Day 1, Cycle 1 until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.	Every 6 weeks from the start of study treatment (Day 1, Cycle 1). Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		Survival status will be collected at 8-week intervals until death, for up to 12 months after the first dose of study medication for the last patient randomized or until the target number of events (deaths) is met, whichever is later.
Safety monitoring including adverse events, vital signs, and laboratory assessments	Standard safety monitoring will be performed and adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03	Through 30 days following last administration of study medication or until initiation of new anticancer treatment

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.
• Collaborators: Taiho Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Giorgio Scagliotti, MD, University of Turin San Luigi Hospital; Principal Investigator: Kaoru Kubota, MD, PhD, Nippon Medical School Hospital Cancer Center

Publications and helpful links

General Publications

• Scagliotti G, Nishio M, Satouchi M, Valmadre G, Niho S, Galetta D, Cortinovis D, Benedetti F, Yoshihara E, Makris L, Inoue A, Kubota K. A phase 2 randomized study of TAS-102 versus topotecan or amrubicin in patients requiring second-line chemotherapy for small cell lung cancer refractory or sensitive to frontline platinum-based chemotherapy. Lung Cancer. 2016 Oct;100:20-23. doi: 10.1016/j.lungcan.2016.06.023. Epub 2016 Jun 27.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: July 12, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimated): July 22, 2013

Study Record Updates

• Last Update Posted (Actual): September 5, 2024
• Last Update Submitted That Met QC Criteria: August 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Second line Small Cell Lung Cancer, (SCLC), Refractory or Sensitive to First line Platinum based chemotherapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan; Amrubicin
• Other Study ID Numbers: TPU-TAS-102-201; 2012-004793-26 (EudraCT Number)