Clinical trial NCT00856830: Bendamustine With Irinotecan Followed by Etoposide/Carboplatin for Patients With Extensive Stage Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Small Cell Lung Cancer
Extensive Stage Lung Cancer
Chemonaive
Keywords: Small cell lung cancer
Chemonaive
Bendamustine
Irinotecan
Etoposide
Carboplatin
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
First posted: 2009-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single arm, open-label, Phase I - II trial with an initial dose escalation component and an expansion cohort of patients treated at the recommended Phase II dose.
Primary purpose: TREATMENT

Brief summary: Small cell lung cancer, or SCLC, constitutes approximately 15% of the 170,000 new cases of lung cancer diagnosed annually in the United States. 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. 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. 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. 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. 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.

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 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.

Primary outcomes:
measure: Number of Participants Experiencing Dose Limiting Toxicity Regimen A - Phase I
timeFrame: 9 weeks
measure: Number of Patients With Adverse Events - Phase II
timeFrame: 9 weeks
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 7 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Marietta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
Study officials:
affiliation: University of Alabama at Birmingham
name: Francisco Robert, M.D.
role: PRINCIPAL_INVESTIGATOR
References: