Bendamustine With Irinotecan Followed by Etoposide/Carboplatin for Patients With Extensive Stage Small Cell Lung Cancer - Full Text View

Sponsor:	University of Alabama at Birmingham
Collaborator:	National Comprehensive Cancer Network
Information provided by (Responsible Party):	Francisco Robert,MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:	NCT00856830

Purpose

SCLC constitutes approximately 15% of the 170,000 new cases of lung cancer diagnosed annually in the United States(1). Extensive-Stage SCLC comprises two thirds of new cases and is generally considered sensitive to chemotherapy, despite a median time to progression of 4 months(2). SCLC is one of the most aggressive and lethal types of cancer, with a median survival of 9 months (range 7-11 months) in patients diagnosed with extensive disease(3). Overall, the majority of patients with SCLC die in less than 2 years (2-year survival rates generally less than 10%), and the 5-year survival rate is 2.3% for patients with extensive disease(4). The regimen of etoposide in combination with a platinum (cisplatin or carboplatin) is generally considered the "standard of care" although a recent Phase III trial suggests improved survival with the combination of cisplatin/irinotecan(5). Further evaluation of new agents in combination regimens attempting to overcome the intrinsic drug resistance seen in extensive-stage SCLC is warranted attempting to improve survival and achieve palliation of disease-related symptoms.

Condition	Intervention	Phase
Small Cell Lung Cancer Extensive Stage Chemonaive	Drug: Bendamustine, Irinotecan, Etoposide/Carboplatin	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/IIa Study of the Novel Combination of Bendamustine With Irinotecan Followed by Etoposide/Carboplatin in Chemonaive Patients With Extensive Stage Small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Bendamustine hydrochloride Bendamustine Etoposide Carboplatin Irinotecan Etoposide phosphate Irinotecan hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum tolerated dose (MTD) and safety of the combination bendamustine and irinotecan in chemotherapy-naive patients with extensive SCLC [ Time Frame: 9 weeks - regimen given every 3 weeks for 3 cycles ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To investigate the time to progression of bendamustine/irinotecan in sequence with etoposide/carboplatin in chemonaive extensive stage SCLC patients. [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	March 2009
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Novel drug combination There is only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.	Drug: Bendamustine, Irinotecan, Etoposide/Carboplatin Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen. All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging. At the end (3 weeks after) of the sixth total round of chemotherapy, subjects will be re-evaluated for response, and will be followed-up for recurrent disease every 8 weeks. Other Names: Irinotecan (Camptosar) Carboplatin (Paraplatin) Etoposide (VdPesid)

Arms

Assigned Interventions

Experimental: Novel drug combination

There is only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.

Drug: Bendamustine, Irinotecan, Etoposide/Carboplatin

Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.

All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
At the end (3 weeks after) of the sixth total round of chemotherapy, subjects will be re-evaluated for response, and will be followed-up for recurrent disease every 8 weeks.

Other Names:

Irinotecan (Camptosar)
Carboplatin (Paraplatin)
Etoposide (VdPesid)

Detailed Description:

We are proposing a novel combination of bendamustine plus irinotecan followed by the standard regimen of etoposide with carboplatin. This will allow the investigation of response to the novel combination as well as any improvement in outcomes compared to historical controls.

Eligibility

Ages Eligible for Study:	18 Years to 79 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologic or cytologic diagnosis of extensive stage SCLC.
Measurable or assessable tumor parameters.
ECOG Performance Status 0-2.
Age between 18 and 79 years (in the State of Alabama > 18).
Adequate bone marrow, liver and renal function, defined as:
Absolute neutrophil count (ANC) ≥ 1500/µL
Hemoglobin ≥ 8g/dl
Platelet count ≥ 100,000/µL
SGOT/SGPT ≤ 2 x upper limit of normal or ≤ 5 x upper limit of normal when liver metastases are present.
Total bilirubin value ≤ 2 x upper limit of normal.
Serum creatinine value ≤ 2 x upper limit of normal.
Fully recovered from any previous surgery (at least 4 weeks since major surgery)
Must have recovered from prior radiation therapy (at least 3 weeks)
All subjects 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.
Must provide written informed consent and authorization to use and disclose health information (HIPAA).
Extensive-stage SCLC as defined as disease not confined to one hemithorax, including ipsilateral pleural effusion or pericardial effusion.
No prior chemotherapy.

Exclusion Criteria:

Concurrent cancer chemotherapy, biologic therapy or radiotherapy.
Administration of any investigational drug within 28 days prior to administration of the current therapy.
Symptomatic brain metastases; those patients should be treated first with either whole brain radiation therapy or radiosurgery.
Concurrent serious infection.
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.
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.
Neuropathy at baseline ≥ Grade 2.
Any evidence or history of hypersensitivity or other contraindications for the drugs used in this trial.
History of chronic diarrhea; or diarrhea (excess of 2-3 stools/day above normal frequency) in the past 2 weeks.
History of a positive serology for human immunodeficiency virus (HIV).
Psychiatric disorder that prevents patients from providing informed consent or following protocol instructions.
Pregnant or lactating women.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856830

Contacts

Contact: Mary Jerome, RN	(205) 934-5092	Mary.Jerome@ccc.uab.edu
Contact: Pam Dixon, RN, OCN, CCRP	205-975-5387	Pam.Dixon@ccc.uab.edu

Locations

United States, Alabama
University of Alabama at Birmingham	Recruiting
Birmingham, Alabama, United States, 35294 - 0104
Principal Investigator: Francisco Robert, M.D.
United States, Georgia
Georgia Cancer Specialists	Recruiting
Marietta, Georgia, United States, 30060
Contact: Roldolfo Bordoni, MD 770-590-8311 rodofo.bordoni@gacancer.com
Principal Investigator: Roldolfo Bordoni, MD

Sponsors and Collaborators

University of Alabama at Birmingham

National Comprehensive Cancer Network

Investigators

Principal Investigator:

Francisco Robert, M.D.

University of Alabama at Birmingham

More Information

No publications provided

Responsible Party:	Francisco Robert,MD, Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:	NCT00856830 History of Changes
Other Study ID Numbers:	F080929010, UAB 0818
Study First Received:	March 5, 2009
Last Updated:	April 19, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:

Small cell lung cancer
Chemonaive
Bendamustine

Irinotecan
Etoposide
Carboplatin

Additional relevant MeSH terms:

Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide
Irinotecan
Etoposide phosphate
Bendamustine

Nitrogen Mustard Compounds
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 24, 2012