Study of Sequential Topoisomerase, Irinotecan/Oxaliplatin - Etoposide /Carboplatin in Extensive SCLC

This study has been completed.
Sponsor:
Collaborators:
Sanofi-Synthelabo
Amgen
Information provided by (Responsible Party):
Francisco Robert,MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00240097
First received: October 13, 2005
Last updated: January 24, 2012
Last verified: October 2010
  Purpose

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.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Irinotecan; Oxaliplatin; Etoposide; Carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Dose-Intense Chemotherapy With Sequential Topoisomerase Targeting With Irinotecan/Oxaliplatin Followed by Etoposide/Carboplatin in Patients With Extensive Small Cell Lung Cancer or Stage IIIb - IV Large Cell Carcinoma of the Lung

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • To determine the objective tumor response rates [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate toxicities, determine the duration of response and time to disease progression and to determine the median survival. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: June 2005
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen A or B of Part I
Chemotherapy-naive patients with extensive SCLC will be treated in one of two regimens: Regimen A consists of treatment with irinotecan and oxaliplatin given every 2 weeks while Regimen B consists of etoposide and carboplatin given every 3 weeks. Both regimens will include re-evaluation for response at least every 8 weeks.
Drug: Irinotecan; Oxaliplatin; Etoposide; Carboplatin
Intervention description:In Part I of the Study(Untreated patients):Patients will be treated with alternating regimens(A and B)--Regimen A:Oxaliplatin-85mg/m2(IV) on day 1 of the cycle plus Irinotecan-150mg/m2(IV) on day 1 of the cycle plus Neulasta 6mg(subc)on day 2 of the cycle,follow by Regimen B: Carboplatin-AUC of 6(IV) on day 15 of the cycle plus Etoposide-100mg/m2(IV) on days 15,16,and 17 of the cycle plus Neulasta-6mg(subc) on day 18 of the cycle.The 2nd cycle will be repeated with Regimen A 3 weeks after the initiation of Regimen B of Cycle 1.A total of 5 cycles will be administered to these patients.In Part II(Relapsed patients):These patients will be treated with Regimen A every 3 weeks for a total of 6-8 cycles of treatment.
Other Names:
  • Irinotecan (Camptosar)
  • Oxaliplatin (Eloxitan)
  • Etoposide (VdPesid)
  • Carboplatin (Paraplatin)
Experimental: Regimen A of Part II
Patients who have either refractory disease or have relapsed from first-line therapy will be treated with Regimen A (described earlier) at 3-week intervals with periodic re-evaluations for response.
Drug: Irinotecan; Oxaliplatin; Etoposide; Carboplatin
Intervention description:In Part I of the Study(Untreated patients):Patients will be treated with alternating regimens(A and B)--Regimen A:Oxaliplatin-85mg/m2(IV) on day 1 of the cycle plus Irinotecan-150mg/m2(IV) on day 1 of the cycle plus Neulasta 6mg(subc)on day 2 of the cycle,follow by Regimen B: Carboplatin-AUC of 6(IV) on day 15 of the cycle plus Etoposide-100mg/m2(IV) on days 15,16,and 17 of the cycle plus Neulasta-6mg(subc) on day 18 of the cycle.The 2nd cycle will be repeated with Regimen A 3 weeks after the initiation of Regimen B of Cycle 1.A total of 5 cycles will be administered to these patients.In Part II(Relapsed patients):These patients will be treated with Regimen A every 3 weeks for a total of 6-8 cycles of treatment.
Other Names:
  • Irinotecan (Camptosar)
  • Oxaliplatin (Eloxitan)
  • Etoposide (VdPesid)
  • Carboplatin (Paraplatin)

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

  Eligibility

Ages Eligible for Study:   19 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologic or cytologic diagnosis of SCLC.
  2. Measurable or assessable tumor parameters.
  3. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00240097

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Sanofi-Synthelabo
Amgen
Investigators
Principal Investigator: Francisco Robert, MD University of Alabama at Birmingham
  More Information

No publications provided by University of Alabama at Birmingham

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Francisco Robert,MD, Professor of Medicine, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00240097     History of Changes
Other Study ID Numbers: F041222002, UAB 0421
Study First Received: October 13, 2005
Last Updated: January 24, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Oxaliplatin
Irinotecan
Etoposide phosphate
Carboplatin
Camptothecin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on September 29, 2014