Radiation With Chemotherapy and a Study Drug to the Para-Aortic Nodes in Cervical Cancer

Cervical Cancer Clinical Trial

Official title:

Phase I Trial of Dose Escalated IMRT to the Para-aortic Nodes With Concurrent Cisplatin and Amifostine in Locally Advanced Cervical Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00137358
• Other study ID #: ETH175-04D
• Status: Withdrawn
• Phase: Phase 1
• First received: August 26, 2005
• Last updated: January 23, 2013

Study information

• Verified date: January 2013
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Investigator has since decided not to pursue this protocol further. No patients were enrolled.

This study is to determine the maximum tolerated dose of external beam radiation to the para-aortic lymph nodes using intensity modulated radiation therapy (IMRT).

This protocol will test the hypothesis that the use of IMRT and amifostine will decrease GI toxicity and therefore allow the radiation dose to the para-aortic lymph nodes to be safely escalated.

Description:

This is a Phase I open-label multi-institutional study that will enroll a minimum of 27 and up to 42 patients with locally advanced cervical cancer (a minimum of 27 will be entered if all dose levels are explored without reaching a dose limiting toxicity at any level). The primary objective is to determine the maximum tolerated dose (MTD) of external beam radiation to the para-aortic lymph nodes using IMRT and amifostine. Patients will be stratified according to gross tumor volume (GTV) prior to dose escalation.

Within each GTV stratum, the dose escalation will be determined as follows: Accrue 3 patients in the first dose level based on the determined stratum. A Dose Limiting Toxicity is defined as the development of > Grade 3 acute GI toxicity, per the RTOG acute toxicity scale. If no DLT is observed at the first dose level, 3 patients will be enrolled at the next dose level. If one patient experiences DLT at a given dose level, 3 additional patients will be enrolled at that dose level. If 0 of these 3 additional patients experience DLT, dosing of the next dose level is begun. If 1 or more of these 3 additional patients experience DLT at the highest dose level below the maximally administered dose, this dose becomes the recommended dose. At least 6 patients must be entered at this recommended dose. The Maximum Tolerated Dose (MTD) is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• No prior therapy other than biopsy of the cervix or endoscopic pelvic nodal resection.

• Patients may have endoscopic resection of enlarged pelvic and low common iliac nodes, however, needle biopsy only of enlarged para-aortic nodes will be eligible for entry.

• Patients with squamous cell, adenocarcinoma, and adenosquamous carcinoma are eligible.

• Patients must have no evidence of metastatic disease outside of the pelvis (except to the para-aortic nodes).

• Patients must have Zubrod performance status 0-1 and no medical contraindications to the administration of full dose chemotherapy.

• Patients must have a life expectancy > 6 months

• Adequate bone marrow function: white blood cell (WBC) 3000/mm3 (absolute neutrophil count [ANC] 1500/mm3); adequate renal function: creatinine 1.5 mg/dl (urinary diversion is permitted to improve renal function); patients must have bilirubin 1.5 mg/dl, ALT 2 x normal.

• No prior (within last 3 years) or simultaneous malignancies (other than basal cell or non-invasive tumors)

Exclusion Criteria:

• Complete resection of the involved para-aortic nodes.

• Patients with evidence of bowel adherent to the GTV by contrast enhanced computed tomography (CT) scan will be ineligible.

• Patients with the following histologies will be ineligible: glassy cell, small cell, carcinoid, adenoid cystic, and clear cell.

• Prior (within last 3 years) malignancies other than basal cell carcinoma or non-invasive malignancies.

• Prior chemotherapy.

• Prior pelvic or abdominal radiation (other than transvaginal irradiation to control bleeding).

• Prior tumor-directed surgery other than lymph node sampling/staging

• Life expectancy < 6 months

• Patients who are pregnant will be ineligible.

• Patients with insulin dependent diabetes will be ineligible.

• Patients who are obese, such that reliable immobilization is not achieved.

• Patients with pain or discomfort that would preclude lying still for extended periods of time.

• Patients with tumors that are bleeding and require more immediate treatment.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Procedure:
• Radiation Therapy

Drug:
• Cisplatin

• Amifostine

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	MedImmune LLC

Country where clinical trial is conducted

United States, 

References & Publications (18)

Aoki T, Nagata Y, Mizowaki T, Kokubo M, Negoro Y, Takayama K, Mitsumori M, Sasai K, Hiraoka M. Clinical evaluation of dynamic arc conformal radiotherapy for paraaortic lymph node metastasis. Radiother Oncol. 2003 Apr;67(1):113-8. — View Citation

Athanassiou H, Antonadou D, Coliarakis N, Kouveli A, Synodinou M, Paraskevaidis M, Sarris G, Georgakopoulos GR, Panousaki K, Karageorgis P, Throuvalas N; Oncology Hellenic Group. Protective effect of amifostine during fractionated radiotherapy in patients with pelvic carcinomas: results of a randomized trial. Int J Radiat Oncol Biol Phys. 2003 Jul 15;56(4):1154-60. — View Citation

Berman ML, Keys H, Creasman W, DiSaia P, Bundy B, Blessing J. Survival and patterns of recurrence in cervical cancer metastatic to periaortic lymph nodes (a Gynecologic Oncology Group study). Gynecol Oncol. 1984 Sep;19(1):8-16. — View Citation

Carl UM, Bahnsen J, Wiegel T. Radiation therapy of para-aortic lymph nodes in cancer of the uterine cervix. Acta Oncol. 1993;32(1):63-7. — View Citation

Gallardo D, Mohar A, Calderillo G, Mota A, Solorza G, Lozano A, Solano P, De La Garza J. Cisplatin, radiation, and amifostine in carcinoma of the uterine cervix. Int J Gynecol Cancer. 1999 May;9(3):225-230. — View Citation

Grigsby PW, Heydon K, Mutch DG, Kim RY, Eifel P. Long-term follow-up of RTOG 92-10: cervical cancer with positive para-aortic lymph nodes. Int J Radiat Oncol Biol Phys. 2001 Nov 15;51(4):982-7. — View Citation

Grigsby PW, Perez CA, Chao KS, Herzog T, Mutch DG, Rader J. Radiation therapy for carcinoma of the cervix with biopsy-proven positive para-aortic lymph nodes. Int J Radiat Oncol Biol Phys. 2001 Mar 1;49(3):733-8. — View Citation

Koukourakis MI, Kyrias G, Kakolyris S, Kouroussis C, Frangiadaki C, Giatromanolaki A, Retalis G, Georgoulias V. Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized phase II study. J Clin Oncol. 2000 Jun;18(11):2226-33. — View Citation

Lepanto P, Littman P, Mikuta J, Davis L, Celebre J. Treatment of para-aortic nodes in carcinoma of the cervix. Cancer. 1975 Jun;35(6):1510-3. — View Citation

Lovecchio JL, Averette HE, Donato D, Bell J. 5-year survival of patients with periaortic nodal metastases in clinical stage IB and IIA cervical carcinoma. Gynecol Oncol. 1989 Jul;34(1):43-5. — View Citation

Malfetano JH, Keys H. Aggressive multimodality treatment for cervical cancer with paraaortic lymph node metastases. Gynecol Oncol. 1991 Jul;42(1):44-7. — View Citation

Mutic S, Malyapa RS, Grigsby PW, Dehdashti F, Miller TR, Zoberi I, Bosch WR, Esthappan J, Low DA. PET-guided IMRT for cervical carcinoma with positive para-aortic lymph nodes-a dose-escalation treatment planning study. Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):28-35. — View Citation

Nori D, Valentine E, Hilaris BS. The role of paraaortic node irradiation in the treatment of cancer of the cervix. Int J Radiat Oncol Biol Phys. 1985 Aug;11(8):1469-73. — View Citation

Podczaski E, Stryker JA, Kaminski P, Ndubisi B, Larson J, DeGeest K, Sorosky J, Mortel R. Extended-field radiation therapy for carcinoma of the cervix. Cancer. 1990 Jul 15;66(2):251-8. — View Citation

Rubin SC, Brookland R, Mikuta JJ, Mangan C, Sutton G, Danoff B. Para-aortic nodal metastases in early cervical carcinoma: long-term survival following extended-field radiotherapy. Gynecol Oncol. 1984 Jun;18(2):213-7. — View Citation

Tewfik HH, Buchsbaum HJ, Latourette HB, Lifshitz SG, Tewfik FA. Para-aortic lymph node irradiation in carcinoma of the cervix after exploratory laparotomy and biopsy-proven positive aortic nodes. Int J Radiat Oncol Biol Phys. 1982 Jan;8(1):13-8. — View Citation

Varia MA, Bundy BN, Deppe G, Mannel R, Averette HE, Rose PG, Connelly P. Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1015-23. — View Citation

Wadler S, Goldberg G, Fields A, Anderson P, Beitler JJ, Sood B, Haynes H, Runowicz C. The potential role of amifostine in conjunction with cisplatin in the treatment of locally advanced carcinoma of the cervix. Semin Oncol. 1996 Aug;23(4 Suppl 8):64-8. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective is to determine the maximum tolerated dose (MTD) of external beam radiation to the para-aortic lymph nodes using IMRT and amifostine.
Secondary	The secondary endpoints include local-regional control, overall survival and toxicity.