Temozolomide as Maintenance Therapy Following Induction Chemotherapy in Extensive Stage Small Cell Lung Cancer

Temozolomide may delay progression in sequence with chemotherapy. This open-label, randomized,multicenter phase II trial was designed to evaluate the role of Temozolomide following 4 or 6 cycles of platinum-based first-line chemotherapy in patients with newly diagnosed estensive-stage SCLC.

Study Overview

• Status: Unknown
• Conditions: Extensive-stage Small Cell Lung Cancer
• Intervention / Treatment: Drug: first-line chemotherapy; Radiation: Prophylactic cranial irradiation; Radiation: thoracic radiotherapy; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cytologically and/or histologically confirmed small-cell lung cancer with extensive-stage disease
• Patients must have measurable disease, this can include brain metastases
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Adequate bone marrow function, as defined by: absolute neutrophil count (ANC) >1,500/µL; platelets >100,000/µL; hemoglobin >=9.0 g/dL
• Normal organ function, defined as follows: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5 × the upper limit of normal (ULN), or AST and ALT <=5 × the ULN if liver function abnormalities are due to underlying malignancy; total serum bilirubin <=1.5 × the ULN; serum creatinine <=1.5 × the ULN
• the time interval from the data of the last chemotherapy to random must be between 3 and 7 weeks
• Women of childbearing potential and men with partners of childbearing potential must agree to use a form of birth control that is acceptable to their physician to prevent pregnancy during treatment
• Patients must be informed of the investigational nature of this study and sign an informed consent form

Exclusion Criteria:

• Patients who are pregnant or breastfeeding
• Patients receiving other investigational agents
• Patients with leptomeningeal involvement
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition or HIV-positive patients on combination antiretroviral therapy. However, HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because these patients are at increased risk of lethal infections when treated with marrow- suppressive therapy. Excluding patients on HAART is necessary due to the potential for pharmacokinetic interactions with temozolomide.

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: BSC group; Patients in the study will receive the following for the duration of the study:First-line chemotherapy according to the NCCN guidelines. The study will consist of 21-day cycles, to a maximum of 6 cycles of therapy for the first-line chemotherapy. Radiotherapy was allowed. Follow-up until disease progression.	Drug: first-line chemotherapy; first-line chemotherapy must be platinum-based: cisplatin(75mg/m2 for d1) or carboplatin（AUC 5 for d1) combined with etoposide（100mg/m2 for d1-d3）; Radiation: Prophylactic cranial irradiation; Prophylactic cranial irradiation was allowed if necessary; Radiation: thoracic radiotherapy; thoracic radiotherapy was allowed if necessary
Experimental: TMZ group; Patients will receive platinum-based first-line chemotherapy according to the NCCN guidelines. The study will consist of 21-day cycles, to a maximum of 6 cyclesfor the first-line chemotherapy. After first-line treatment, temozolomide will be given alone as maintenance therapy in all patients who have achieved study entry hematologic criteria and who do not have progressive disease or severe toxicity. During temozolomide maintenance therapy, patients will receive temozolomide at 150mg/m2/d for 5 days of a 28-day cycle orally daily. Temozolomide maintenance therapy will continue until progressive disease or irreversible toxicity occurs. Re-staging will be performed every 2 cycles (every 8 weeks) during the study, radiotherapy was allowed.	Drug: first-line chemotherapy; first-line chemotherapy must be platinum-based: cisplatin(75mg/m2 for d1) or carboplatin（AUC 5 for d1) combined with etoposide（100mg/m2 for d1-d3）; Radiation: Prophylactic cranial irradiation; Prophylactic cranial irradiation was allowed if necessary; Radiation: thoracic radiotherapy; thoracic radiotherapy was allowed if necessary; Drug: Temozolomide; Temozolomide is a nonclassic oral alkylating agent. Temozolomide will be given alone as maintenance therapy in patients who have achieved study entry hematologic criteria and who do not have progressive disease or severe toxicity. During temozolomide maintenance therapy, patients will receive temozolomide at 150mg/m2/d for 5 days of a 28-day cycle orally daily. Temozolomide maintenance therapy will continue until progressive disease or irreversible toxicity occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS of the maintenance therapy	from the data of randomized to the date of disease progression or the patient dies	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	from the date of first-line chemotherapy to the date of disease progression	2 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	2 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: May 7, 2016
• First Submitted That Met QC Criteria: May 12, 2016
• First Posted (Estimate): May 13, 2016

Study Record Updates

• Last Update Posted (Estimate): May 17, 2016
• Last Update Submitted That Met QC Criteria: May 15, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Small Cell Lung Carcinoma
• 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; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: 301PLAGH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED