Study of Sequential Topoisomerase, Irinotecan/Oxaliplatin - Etoposide /Carboplatin in Extensive Small Cell Lung Cancer (SCLC)

NCT ID: NCT00240097

Last Updated: 2014-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2010-06-30

Brief Summary

The primary objective of Part I of the study is to determine tumor response rate of sequential topoisomerase targeting with irinotecan/oxaliplatin followed by etoposide /carboplatin in chemotherapy-naïve patients with extensive small cell lung cancer. The primary objective of Part II of the study is to determine the objective tumor response rate of irinotecan/oxaliplatin in patients with either refractory disease or who have relapsed to first line chemotherapy or chemoradiotherapy.

Detailed Description

This is a Phase II, open label study for either chemotherapy-naïve patients with extensive SCLC or patients who are refractory or have relapsed to 1st line therapy for SCLC. The primary objective is to determine the objective response rate.

This study consists of 2 parts:

Part I - Chemotherapy-naïve patients with extensive SCLC

• These patients will be treated with sequential topoisomerase targeting regimens (Regimen A and B). Regimen A consists of irinotecan and oxaliplatin (IROX), given on Day 1, and Neulasta administered on Day 2. Regimen B consists of etoposide and carboplatin, given on Day 15(etoposide will be given daily x 3)and Neulasta on Day 18. Then, Regimen A will be given again 3 weeks later. The first re-evaluation for response will be performed 3 weeks after the second round of the sequential regimens.

Schema of Part I:

Regimen A (→ 2 weeks) Regimen B (→ 3 weeks) Regimen A (→ 2 weeks) Regimen B → (3 weeks) → Re-Stage

• The second re-evaluation for response will be performed 3 weeks after the fourth round of the sequential regimen. At this point patients with stable disease will be observed; those with either a partial or complete response will be treated with another round of sequential therapy (Regimen A → Regimen B) if there is no evidence of unacceptable toxicity. At the end (3 weeks after) of the fifth round of chemotherapy, patients will be re-evaluated for response, and will be followed-up for recurrent disease every 8 weeks.
• Analysis of Top I and Top II levels in peripheral blood mononuclear cells will be performed in 10 patients of Part I.
• Evaluation of the expression of the ERCC genes (ERCC1, ERCC2, and XPF) will be performed in those patients in Part I with an adequate tumor specimen.

Part II - Patients who have either refractory disease or have relapsed from 1st line therapy

• These patients will be treated with Regimen A1 (IROX) at 3-week intervals. Neulasta will be administered on Day 2 of each cycle. The first re-evaluation for response will be performed 3 weeks after the 3rd cycle of Regimen A1. The second re-evaluation for response will be performed 3 weeks after the 6th cycle of Regimen A1. At this point, patients with stable disease will be observed; those with either a partial or complete response will be treated with two additional cycles of Regimen A1 if there is no evidence of unacceptable toxicity. At the end (3 weeks after) of the 8th cycle of Regimen A1, patients will be re-evaluated for response, and will be followed-up for recurrent disease every 8 weeks.

Schema of Part II:

Regimen A1 (→ 3 weeks) Regimen A1 (→ 3 weeks) Regimen A1 (→ 3 weeks) Re-Stage

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Irinotecan; Oxaliplatin; Neulasta

Irinotecan (I.V.) 150-200 mg/m2; Day 1 (every 5 weeks) Oxaliplatin (I.V.) 85 mg/m2; Day 1 (every 5 weeks) Neulasta (subcutaneous) 6 mg; Day 1 (every 5 weeks)

Group Type: EXPERIMENTAL

Intervention A: Irinotecan; Oxaliplatin; Neulasta

Intervention Type: DRUG

Irinotecan (I.V.) 150-200 mg/m2; Day 1 (every 5 weeks) Oxaliplatin (I.V.) 85 mg/m2; Day 1 (every 5 weeks) Neulasta (subcutaneous) 6 mg; Day 1 (every 5 weeks)

Etoposide; Carboplatin; Neulasta

Etoposide (I.V.) 100 mg/m2; Day 1, 2, 3 (every 5 weeks) Carboplatin (I.V.) area under the concentration curve (AUC) 6; Day 1 (every 5 weeks) Neulasta (subcutaneous) 6 mg; Day 4 (every 5 weeks)

Group Type: EXPERIMENTAL

Intervention B: Etoposide; Carboplatin; Neulasta

Intervention Type: DRUG

Etoposide (I.V.) 100 mg/m2; Day 1, 2, 3 (every 5 weeks) Carboplatin (I.V.) AUC 6; Day 1 (every 5 weeks) Neulasta (subcutaneous) 6 mg; Day 4 (every 5 weeks)

Interventions

Intervention A: Irinotecan; Oxaliplatin; Neulasta

Irinotecan (I.V.) 150-200 mg/m2; Day 1 (every 5 weeks) Oxaliplatin (I.V.) 85 mg/m2; Day 1 (every 5 weeks) Neulasta (subcutaneous) 6 mg; Day 1 (every 5 weeks)

Intervention Type: DRUG

Intervention B: Etoposide; Carboplatin; Neulasta

Etoposide (I.V.) 100 mg/m2; Day 1, 2, 3 (every 5 weeks) Carboplatin (I.V.) AUC 6; Day 1 (every 5 weeks) Neulasta (subcutaneous) 6 mg; Day 4 (every 5 weeks)

Intervention Type: DRUG

Other Intervention Names

Camptosar; Eloxatin; Pegfilgrastim; VP-16; Etopophos®; Vepesid®; Taxol; Paraplatin; Pegfilgrastim

Eligibility Criteria

Inclusion Criteria

1. Histologic or cytologic diagnosis of SCLC.

2. Measurable or assessable tumor parameters.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

4. Age between 18 and 79 years (in the State of Alabama > 18).

5. Adequate bone marrow, liver and renal function, defined as:

• Absolute neutrophil count (ANC) ≥ 1500/µL
• Platelet count ≥ 100,000/µL
• SGOT/SGPT ≤ 2.5 x upper limit of normal or ≤ 5 x upper limit of normal when liver metastases are present.
• Total bilirubin value ≤ 1.5 x upper limit of normal.
• Serum creatinine value ≤ 1.5 x upper limit of normal.

6. Fully recovered from any previous surgery (at least 4 weeks since major surgery)

7. Must have recovered from prior radiation therapy (at least 3 weeks)

8. All participants must agree to practice approved methods of birth control (if applicable). A negative pregnancy test must be documented during the screening period for women of childbearing potential.

9. Must provide written informed consent and authorization to use and disclose health information (HIPAA).

For Part I

10. Extensive-stage SCLC as defined as disease not confined to one hemithorax, including ipsilateral pleural effusion or pericardial effusion.

11. No prior chemotherapy.

For Part II

12. Patients with either refractory disease, or who have relapsed 1st line therapy. No prior chemotherapy with Oxaliplatin or irinotecan.

13. Demonstrated tumor progression at the time of study entry.

Exclusion Criteria

1. Concurrent cancer chemotherapy, biologic therapy or radiotherapy.

2. Administration of any investigational drug within 28 days prior to administration of the current therapy.

3. Symptomatic brain metastases; those patients should be treated first with either whole brain radiation therapy or radiosurgery.

4. Concurrent serious infection.

5. Concomitant severe or uncontrolled underlying medical disease unrelated to the tumor, which is likely to compromise patient safety and affect the outcome of the study.

6. History of other malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for a minimum of 2 years.

7. Neuropathy at baseline ≥ Grade 2.

8. Any evidence or history of hypersensitivity or other contraindications for the drugs used in this trial.

9. History of chronic diarrhea; or diarrhea (excess of 2-3 stools/day above normal frequency) in the past 2 weeks.

10. History of a positive serology for human immunodeficiency virus (HIV).

11. Psychiatric disorder that prevents patients from providing informed consent or following protocol instructions.

12. Pregnant or lactating women.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi-Synthelabo

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Francisco Robert,MD

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francisco Robert, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

References

Rossman J, Reddy V, Cantor A, Miley D, Robert F. Phase II study of dose-intense chemotherapy with sequential topoisomerase-targeting regimens with irinotecan/oxaliplatin followed by etoposide/carboplatin in chemotherapy naive patients with extensive small cell lung cancer. Lung Cancer. 2011 May;72(2):219-23. doi: 10.1016/j.lungcan.2010.08.023. Epub 2010 Oct 8.

Reference Type: DERIVED

PMID: 20934233 (View on PubMed)

Other Identifiers

UAB 0421

Identifier Type: OTHER

Identifier Source: secondary_id

F041222002

Identifier Type: -

Identifier Source: org_study_id