Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Treatment Closed 18 and over NCI NCI-86-C-92A NCI-NMOB-855, NCI-T86-0137N, T86-0137

Objectives

I.  Determine the overall and complete response rate, pulmonary toxicity, and 
survival of patients with limited stage small cell carcinoma of the lung 
(SCCL) given etoposide/cisplatin (VP-16/CACP) plus simultaneous twice-daily 
chest irradiation.

II.  Determine, in a consecutive series of patients with limited stage SCCL, 
the frequency with which adequate cancer tissue for drug testing can be safely 
obtained using a thoracic surgical procedure.

III.  Determine the frequency with which data on in vitro drug sensitivity of 
each individual patient's tumor can be obtained in the above patients.

IV.  Determine whether the ability to establish tumor cell lines in vitro and 
the in vitro sensitivity of these lines to VP-16, CACP, and a combination of 
the two drugs are correlated with overall and complete response rates and 
complete response duration in patients treated with VP-16/CACP.

V.  Determine whether changes in vitro drug sensitivity compared to 
pretreatment findings occur in cell lines from tumor biopsies obtained after 
12 weeks of therapy with VP-16/CACP and after the development of tumor 
progression.

VI.  Determine the frequency of objective response to a single drug chosen on 
the basis of the in vitro drug sensitivity of a tumor biopsy obtained at the 
time of tumor progression and administered after the patient has either failed 
to respond to or has progressed on appropriate therapy initiated after the 
tumor biopsy was obtained.

Entry Criteria

Disease Characteristics:

Histologically confirmed small cell lung carcinoma or mixed
small cell/large cell carcinoma

  Primary pulmonary lesion required, but patients with
  non-pulmonary small cell cancer arising in an extrapulmonary
  site with no tumor extension beyond regional lymph nodes may
  be treated on this protocol and the results reported
  separately

Limited disease required, defined as:

  Disease confined to one hemithorax, the mediastinum, and
  ipsilateral or contralateral supraclavicular nodes and
  encompassable in a tolerable radiotherapy port

  Bilateral endobronchial disease found on fiberoptic
  bronchoscopy

No extensive disease, defined as:
  Chest wall involvement
  Significant pleural effusion (regardless of cytology)
  Pathologic pleural involvement
  Pericardial tumor
  Clinically significant pericardial effusion

Lack of evaluable disease (e.g., resected primary lung tumor)
allowed

  Patients with non-evaluable disease are treated and followed
  for survival, but not included in response rate calculations

Refusal of elective thoracotomy (used to obtain tissue for drug
sensitivity testing) allowed

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy for small cell lung cancer

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy for small cell lung cancer

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0-2

Hematopoietic:
  WBC more than 4,000
  Platelets more than 100,000

Hepatic:
  Not specified

Renal:
  Creatinine less than 2.0 mg/dl

Cardiovascular:
  No less than fully compensated CHF
  No significant arrhythmia
  No MI within 3 months
  No other symptomatic heart disease

Pulmonary:
  pO2 at least 50 mm Hg (on room air)
  pCO2 no more than 50 mm Hg (on room air)

Other:
  No uncontrolled major active infection not due to an 
     obstructed bronchus
  Willing to receive blood product transfusions
  No second malignancy except:
     Nonmelanomatous skin cancer
     Carcinoma in situ of the cervix
  No major psychiatric problems

Expected Enrollment

60 patients will be required, and accrual is expected to proceed at a rate of 
12 patients/year over 4 years.

Outline

Nonrandomized study.  All patients are treated on Induction and (if indicated) 
CNS Therapy.  Patients with in vitro drug sensitivity data available are then 
treated on one of the In Vitro Drug Sensitivity Regimens (Regimens A through 
M), as indicated.  Patients with no in vitro drug sensitivity data available 
are treated on Regimen A.

Induction:  2-Drug Combination Chemotherapy plus Radiotherapy.  Etoposide, 
VP-16, NSC-141540; Cisplatin, CACP, NSC-119875; plus chest irradiation using 
megavoltage equipment.

CNS Therapy:  Radiotherapy.  Prophylactic cranial irradiation.

In Vitro Drug Sensitivity Regimens.

Regimen A:  3-Drug Combination Chemotherapy.  VAC:  Vincristine, VCR, 
NSC-67574; Doxorubicin, Adriamycin, ADR, NSC-123127; Cyclophosphamide, CTX, 
NSC-26271.

Regimen B:  3-Drug Combination Chemotherapy.  CTX; ADR; Methotrexate, MTX, 
NSC-740.

Regimen C:  3-Drug Combination Chemotherapy.  CTX; ADR; VP-16.

Regimen D:  3-Drug Combination Chemotherapy.  CTX; ADR; CACP.

Regimen E:  3-Drug Combination Chemotherapy.  CTX; MTX; VCR.

Regimen F:  3-Drug Combination Chemotherapy.  CTX; VCR; Lomustine, CCNU, 
NSC-79037.

Regimen G:  3-Drug Combination Chemotherapy.  CTX; MTX; VP-16.

Regimen H:  3-Drug Combination Chemotherapy.  CTX; MTX; CCNU.

Regimen I:  3-Drug Combination Chemotherapy.  CTX; CACP; VP-16.

Regimen J:  3-Drug Combination Chemotherapy.  ADR; VCR; VP-16.

Regimen K:  3-Drug Combination Chemotherapy.  ADR; MTX; VP-16.

Regimen L:  3-Drug Combination Chemotherapy.  ADR; CACP; VP-16.

Regimen M:  3-Drug Combination Chemotherapy.  VCR; MTX; VP-16.

Johnson BE, Bridges JD, Sobczeck M, et al.: Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine. J Clin Oncol 14 (3): 806-13, 1996.[PUBMED Abstract]

Gray JR, Sobczak ML, Hahn SM, et al.: Analysis of local control in 150 limited stage small cell lung cancer patients treated with combined thoracic irradiation and multiagent chemotherapy. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1056, 349, 1995.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Bruce Johnson, MD, Protocol chair		Ph: 617-632-4790; 866-790-4500