Current Clinical Trials in Small-Cell Lung Cancer

Lung cancer is the number one cause of cancer death for both men and women in the United States. In the year 2001, it is estimated that 170,000 new cases of lung cancer will be diagnosed, approximately 20% of which will be small-cell lung cancer.

Clinical Trials Referral Resource is designed to serve as a ready reference for oncologists to help identify clinical trials that might be suitable for their patients. We hope it will also enhance accrual to clinical trials by informing practicing oncologists of ongoing protocols. Currently in the United States less than 10% of eligible adult patients are entered into clinical trials. The result is a delay in answering important therapeutic and scientific questions and disseminating therapeutic advances to the general oncology community.

It should be emphasized that including a specific trial does not imply that it is more important than another trial. Among the criteria for selection are that the trial is addressing an important question and is not expected to close in the immediate future (less than 1 year), and that initial staging or laboratory tests required for patient eligibility are widely practiced and available. Information on other protocols can be accessed via Physician’s Data Query (PDQ).*

We emphasize that this is an attempt to encourage referral of patients to these trials. We are specifically not soliciting additional members for the cooperative groups, nor are we suggesting how practicing oncologists should be treating patients who are not in a study.

This month’s installment of Clinical Trials Referral Resource is devoted to studies in small-cell lung cancer.

For patient entry information, see the individual trials.

* PDQ is a comprehensive database service provided by the National Cancer Institute’s International Cancer Information Center and Office of Cancer Communications for retrieval of cancer treatment information, including peer-reviewed statements on treatment options, supportive care, screening, and prevention; and an international clinical trials registry. For more information on PDQ, Internet access is available at http://cancernet.nci.nih.gov/pdqfull.html, or contact the Cancer Information Service offices (1-800-4-CANCER).

Little progress has been made in this disease in the last decade. Patients with limited disease are generally treated with cisplatin (Platinol)-based combination chemotherapy and radiotherapy, with a 5-year survival rate of approximately 20%. Patients with extensive disease are also treated with cisplatin-based combination chemotherapy, but the median survival duration for these patients is only 8 to 10 months, and long-term survival is rare. Clearly, current therapies are not satisfactory, and all patients should be considered for participation in well-designed clinical trials.[1-5]

A variety of novel drugs have been investigated as single agents in patients with small-cell lung cancer. Taxanes, particularly paclitaxel (Taxol) have promising activity and are currently being investigated in combination with cisplatin and etoposide in a randomized trial in patients with extensive disease. The topoisomerase I inhibitors topotecan (Hycamtin) and irinotecan (CPT-11, Camptosar) also have single-agent activity and are being explored in combination with other agents in phase II trials. There are now a number of agents available that interfere with specific pathways or receptors both within and external to the malignant cell.

A variety of molecules are potential targets for therapy in small-cell lung cancer, including myc, p53, and Rb oncogenes as well as neuroendocrine, apoptotic, and angiogenic pathways. Several of these targeted therapies are currently being investigated in clinical trials and may hold promise. Many of these targets and potential new therapies were discussed in detail at a recent National Cancer Institute (NCI)-sponsored State of the Science meeting entitled "Molecular Targets for Therapy in Small-Cell Lung Cancer." Interested individuals can review the proceedings of this meeting on the Web at http://www.conference-cast.com/webtie/sots/sots.htm.

The following list includes approved and/or active protocols for patients with newly diagnosed small-cell lung cancer as well as studies for patients with recurrent disease sponsored by the Division of Cancer Treatment and Diagnosis of the NCI.

Phase III

Title: A Phase III, Double-Blind, Randomized Study of the Effect of Megestrol Acetate on Weight and Health-Related Quality of Life in Lung Cancer Patients Receiving Thoracic Radiation Therapy
Protocol Number: 892
Participating Institutions: Wake Forest University Comprehensive Cancer Center, East Carolina University, Greenville CCOP, Southeast Cancer Control Consortium CCOP, Upstate Carolina CCOP, Virginia Commonwealth University
Protocol Status: In review
Contact: Edward G. Shaw, MD, (336) 716-4647

Title: Phase III Randomized Study of Etoposide and Cisplatin With or Without Paclitaxel in Patients With Extensive Stage Small Cell Lung Cancer
Protocol Number: 9732
Participating Institutions: Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, North Central Cancer Treatment Group, Southwest Oncology Group
Protocol Status: Active
Contact: Harvey B. Niell, Cancer and Leukemia Group B, (901) 528-5798; for a complete listing of study contacts, click hereLatest Information:http://cancernet.nci.nih.gov/

Title: Phase III Randomized Study of Donepezil and Vitamin E in the Prevention of Cognitive Dysfunction Following Cancer Treatment That Included Prophylactic Cranial Irradiation in Patients With Small Cell Lung Cancer
Protocol Number: N99C5
Participating Institution: North Central Cancer Treatment Group
Protocol Status: Active
Contact: Aminah Jatoi, North Central Cancer Treatment Group, (507) 284-2511; for a complete listing of study contacts, click hereLatest Information:http://cancernet.nci.nih.gov/

Phase II

Title: Phase II Study of Chloroquinoxaline Sulfonamide in Patients With Platinum-Refractory Small Cell Lung Cancer
Protocol Number: 57
Participating Institutions: University of California at Davis
Protocol Status: Active
Contact: Primo N. Lara, University of California Davis Cancer Center, (916) 734-3772
Latest Information:http://cancernet.nci.nih.gov/

Title: Phase II Study of FR901228 in Patients With Refractory or Progressive Small Cell or Non-Small Cell Lung Cancer
Protocol Number: 1053
Participating Institutions: National Cancer Institute Surgery Branch
Protocol Status: Active
Contact: David S. Schrump, Surgery Branch, (301) 496-2127
Latest Information:http://cancernet.nci.nih.gov/

Title: Phase II Study of Paclitaxel in Patients With Extensive Stage Small Cell Lung Cancer
Protocol Number: 39901
Participating Institutions: Ellis Fischel Cancer Center - Columbia
Protocol Status: Active
Contact: Michael C. Perry, Ellis Fischel Cancer Center - Columbia, (573) 882-4979
Latest Information:http://cancernet.nci.nih.gov/

Title: Phase II Study of Gemcitabine Plus Irinotecan in Patients With Recurrent or Refractory Small Cell Lung Cancer
Protocol Number: CLB-39902
Participating Institution: Cancer and Leukemia Group B
Protocol Status: Active
Contact: Caio Max S. Rocha Lima, Cancer and Leukemia Group B, (843) 792-4271; for a complete listing of study contacts, click hereLatest Information:http://cancernet.nci.nih.gov/

Title: Phase II Study of Topotecan and Paclitaxel in Patients With Recurrent or Refractory Small Cell Lung Cancer
Protocol Number: NCCTG-972051
Participating Institution: North Central Cancer Treatment Group
Protocol Status: Active
Contact: James R. Jett, North Central Cancer Treatment Group, (507) 284-3764; for a complete listing of study contacts, click hereLatest Information:http://cancernet.nci.nih.gov/

Title: A Phase II Randomized Trial With Captopril (Capoten) in Patients Who Have Received Radiation Therapy ± Chemotherapy for Stage II-IIIA Non-Small-Cell Lung Cancer or Limited-Stage Small-Cell Lung Cancer
Protocol Number: RTOG-L-0123
Participating Institutions: Radiation Therapy Oncology Group, Northwestern Memorial Hospital
Protocol Status: In review
Contact: Elaine Pakuris, (215) 574-3195

Title: Phase II Study of Paclitaxel, Carboplatin, Topotecan, and Filgrastim (G-CSF) in Patients With Previously Untreated Extensive Stage Small Cell Lung Cancer
Protocol Number: S9914
Participating Institution: Southwest Oncology Group
Protocol Status: Active
Contact: Frank Dunphy, Southwest Oncology Group, (919) 684-5808; for a complete listing of study contacts, click hereLatest Information:http://cancernet.nci.nih.gov/

Title: Phase II Study of Fenretinide in Patients With Recurrent Small Cell Lung Cancer
Protocol Number: T99-0112
Participating Institutions: University of Michigan Comprehensive Cancer Center
Protocol Status: Active
Contact: Gregory P. Kalemkerian, University of Michigan Comprehensive Cancer Center, (734) 936-5281
Latest Information:http://cancernet.nci.nih.gov/

Phase I/II

Title: Phase I/II Study of Topotecan and Paclitaxel Preceding and Following High Dose Thoracic Radiotherapy With Concurrent Cisplatin, Etoposide, and Amifostine in Patients With Limited Stage Small Cell Lung Cancer
Protocol Number: N9923
Participating Institution: North Central Cancer Treatment Group
Protocol Status: Active
Contact: Scott Okuno, North Central Cancer Treatment Group, (507) 284-2511; for a complete listing of study contacts, click hereLatest Information:http://cancernet.nci.nih.gov/

Title: A Phase I/II Dose Escalation Study of Thoracic Irradiation With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer
Protocol Number: RTOG-97-12
Participating Institution: Radiation Therapy Oncology Group
Protocol Status: In review
Contact: Elaine Pakuris, (215) 574-3195

Title: A Phase I/II Study of G3139, a BCL-2 Antisense Oligonucleotide, Combined With Paclitaxel for the Treatment of Recurrent Small-Cell Lung Cancer
Protocol Number: T98-0091
Participating Institutions: University of Chicago, Lutheran General Hospital, University of Illinois, Weiss Memorial Hospital, Decatur Memorial Hospital, Oncology-Hematology Associates, Kellogg Cancer Center- Evanston Hospital, Michiana Hematology-Oncology Professional Corporation, Ohio State University Hospital, Fort Wayne Medical Oncology-Hematology Incorporated, Central Illinois Hematology Oncology Center
Protocol Status: In review
Contact: Charles M. Rudin, MD, (773) 702-9306

Phase I

Title: Phase I Study of Tirapazamine, Cisplatin, and Etoposide Concurrently With Radiotherapy in Patients With Limited Stage Small Cell Lung Cancer
Protocol Number: SWOG-0004
Participating Institution: Southwest Oncology Group
Protocol Status: Active
Contact: Quynh-Thu Le, Southwest Oncology Group, (650) 723-6171; for a complete listing of study contacts, click hereLatest Information:http://cancernet.nci.nih.gov/

Title: Phase I Study of Decitabine Mediated Induction of Tumor Antigen and Tumor Suppressor Gene Expression in Patients With Unresectable Lung or Esophageal Cancer, or Malignant Pleural Mesothelioma
Protocol Number: T99-0012
Participating Institution: National Cancer Institute Surgery Branch
Protocol Status: Active
Contact: David S. Schrump, Surgery Branch, (301) 496-2127
Latest Information:http://cancernet.nci.nih.gov/

Other

Title: Detection of Tumor Cells in Marrow and Blood of Patients With Limited-Stage Small-Cell Lung Cancer at Diagnosis and After First Response
Protocol Number: CALGB-159803
Participating Institution: Cancer and Leukemia Group B
Protocol Status: In review
Contact: CALGB Central Office, (773) 702-9171

References:

1. Greenle R, Taylor M, Bolden S, et al: Cancer statistics 2000. CA Cancer J Clin 50:7-33, 2000.

2. Clinical Trial Service Unit, Radcliffe Infirmary, Oxford. Adjuvant tamoxifen longer against shorter (ATLAS). Protocol. April, 1995. ATLAS Office, Clinical Trials Service Unit. Radcliffe Infirmary, Oxford OX2 6HE, UK.

3. CRC Trials Unit, Birmingham. Adjuvant tamoxifen treatment offer more? (aTTom). Protocol. CRC Trials Unit, Clinical Research Block, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.

4. Norton L, Slamon D, Leyland-Jones B, et al: Overall survival advantage to simultaneous chemotherapy plus the humanized anti-HER2 monoclonal antibody Herceptin in HER2-overexpressing metastatic breast cancer (abstract). Proc Am Soc Clin Oncol 18:127a, 1999.

5. Mundy GR: Mechanisms of bone metastasis. Cancer 80(suppl 8):1546-1556, 1997.

6. Mundy G: Bisphosphonates and anticancer drugs. New Engl J Med 339(6):398-400, 1998.

7. Diel I, Solomyer EF, Costa S, et al: Reduction in new metastases in breast cancer with adjuvant clodronate treatment. New Engl J Med 339:357-363, 1998.

8. Powles TJ, Paterson AHG, Neventaus S, et al: Adjuvant clodronate reduces the incidence of bone metastases in patients with primary operable breast cancer (abstract). Proc Am Soc Clin Oncol 17:468a, 1998.

9. Saarto T, Blomqvist C, Virkkunen P, et al: No reduction of bone metastases with adjuvant clodronate in node-positive breast cancer patients (abstract). Proc Am Soc Clin Oncol 18:489a, 1999.

10. Henderson JC, Berry D, Demetri G, et al: Improved disease-free and overall survival from the addition of sequential paclitaxel but not from the escalation of doxorubicin dose level in the adjuvant chemotherapy of patients with node-positive primary breast cancer (abstract). Proc Am Soc Clin Oncol 17:101a, 1998.

11. Overgaard M, Hansen PS, Overgaard J, et al: Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 337(14):949-55, 1997.

12. Overgaard M, Jensen MB, Overgaard J, et al: Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 353(9165):1641-1648, 1999.

13. Ragaz J, Jackson SM , Le N, et al: Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 337:956-962, 1997.

14. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG): Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of randomised trials. Lancet 355:1757-1770, 2000.