Clinical trial NCT00006012: Combination Chemotherapy and Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer
Official title: Phase I-II Study of Topotecan and Paclitaxel Followed by High-Dose Thoracic Radiation Therapy With Concomitant Cisplatin/Etoposide and Amifostine in Limited-Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Drug/Agent Toxicity by Tissue/Organ
Lung Cancer
Radiation Toxicity
Keywords: drug/agent toxicity by tissue/organ
radiation toxicity
limited stage small cell lung cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-08
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy before, during, and after radiation therapy in treating patients who have limited-stage small cell lung cancer.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of thoracic radiotherapy administered with cisplatin, etoposide, and amifostine preceded and followed by topotecan and paclitaxel in patients with limited stage small cell lung cancer (phase I closed to accrual as of 5/27/2004).
* Determine the two-year survival of this patient population treated with this regimen.
* Determine the two-year, progression-free local control rate in this patient population treated with this regimen.
* Assess the tolerability of this treatment regimen in these patients.
* Determine the antitumor activity of this regimen in these patients.
* Determine the overall survival and overall time to progression in this patient population treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of thoracic radiotherapy (TRT).

Patients receive topotecan IV on days 1-5 and paclitaxel IV over 3 hours on day 5. Patients receive filgrastim (G-CSF) subcutaneously (SC) daily beginning 24 hours after the last dose of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 2 courses.

After 2 courses of topotecan and paclitaxel, patients undergo TRT twice daily for 5 consecutive days for 5 weeks. During TRT, patients receive cisplatin IV, oral etoposide, and amifostine SC daily prior to TRT.

At 4 weeks after completion of TRT, patients receive 2 additional courses of topotecan, paclitaxel, and G-CSF every 3 weeks followed by prophylactic cranial irradiation.

Cohorts of 3-6 patients receive escalating doses of TRT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity (phase I closed to accrual as of 5/27/2004).

Patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 3-73 patients will be accrued for this study (phase I closed to accrual as of 5/27/2004).

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed small cell lung cancer
* Limited disease confined to one hemithorax, the ipsilateral supraclavicular fossa, and encompassable within tolerable thoracic radiotherapy field

  * Minimal pleural effusions (i.e., blunting of the costophrenic angle on chest x-ray or a small effusion on CT scan) allowed
* Measurable disease

  * At least one lesion accurately measured in at least 1 dimension with longest diameter at least 20 mm

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 12 weeks

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* AST no greater than 3 times ULN

Renal:

* Creatinine no greater than 1.5 times ULN

Cardiovascular:

* No New York Heart Association class III or IV heart disease

Pulmonary:

* FEV_1 at least 40% of predicted AND at least 1 liter

Other:

* No uncontrolled infection
* No other severe underlying diseases
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas (carcinoma in situ)
* No grade 2 or greater peripheral neuropathy
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No hypersensitivity to E.coli-derived proteins, filgrastim (G-CSF), or any excipients of G-CSF

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* No prior hemithorax radiotherapy

Surgery

* Not specified

Other

* No prior therapy for small cell lung cancer

Primary outcomes:
measure: Survival at 2 years
timeFrame: at 2 years
Secondary outcomes:
measure: Local progression-free survival at 2 years
timeFrame: at 2 years
measure: Overall survival
timeFrame: Up to 5 years
measure: Time to progression
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Mayo Clinic Scottsdale Oncology Program
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: InterCommunity Cancer Center of Western Illinois
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology Hematology Associates, Limited - West
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology/Hematology Associates of Central Illinois, P.C.
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Valley Cancer Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, P.C.
state: Iowa
city: Cedar Rapids
country: United States
facility: St. Luke's Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Cancer Center at Mercy Medical Center
state: Iowa
city: Mason City
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - North Iowa
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, P.A. - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, P.A. - Parsons
state: Kansas
city: Pratt
country: United States
facility: Pratt Cancer Center of Kansas
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, P.A.
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, P.A. - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Bemidji
country: United States
facility: MeritCare Clinic - Bemidji
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Lincoln
country: United States
facility: Bryan LGH Medical Center West
state: Nebraska
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Lincoln
country: United States
facility: St. Elizabeth Regional Medical Center
state: Nebraska
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Cancer Care Center at Medcenter One Hospital
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, P.C.
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center
state: North Dakota
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Medical Group
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Cancer Center at Altru Hospital
state: North Dakota
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sioux Valley Hospital and University of South Dakota Medical Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera McKennan Hospital and University Health Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center
state: South Dakota
city: La Crosse
country: United States
facility: Franciscan Skemp Healthcare
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Scott Okuno, MD
role: STUDY_CHAIR
References:
citation: Garces YI, Okuno SH, Schild SE, Mandrekar SJ, Bot BM, Martens JM, Wender DB, Soori GS, Moore DF Jr, Kozelsky TF, Jett JR. Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):995-1001. doi: 10.1016/j.ijrobp.2006.10.034.
citation: Garces YI, Okuno SH, Schild SE, et al.: A phase I/II NCCTG trial of escalating doses of twice daily thoracic radiation therapy (TRT) in limited-stage small cell lung cancer (LSCLC). [Abstract] J Clin Oncol 23 (Suppl 16): A-7163, 661s, 2005.