Weekly IV Topotecan and Cisplatin With Radiation in Cervical Carcinoma

NCT ID: NCT00257816

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2007-12-17

Brief Summary

There will be approximately 14,000 new patients with invasive cervical cancer diagnosed in the United States in 2003 with about 4,000 deaths from this disease. This accounts for approximately 17% of all deaths due to gynecologic cancers. Radiation has been the primary treatment modality for locoregionally advanced cervical cancer. Recent trials of concomitant systemic cisplatin chemotherapy and radiation have shown high response rates (RR) with improvements in durable remissions and overall survival. Though the incidence and mortality in the U.S. dropped steadily from years 1940 to 2000, there has recently been a plateau, arresting the decline. With the routine addition of systemic Cisplatin (CDDP) chemotherapy to local regional radiation, mortality from advanced cervical cancer in the United States is expected to further decrease. However, further advances in this disease are needed.

Detailed Description

All eligible patients with invasive squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix, Stages I-B2, II-B, III-B, and IV-A, will experience clinical staging as permitted by FIGO staging criteria.

Primary Objective:

Feasibility and toxicity of administering weekly Topotecan among patients with carcinoma of the cervix receiving concurrent pelvic radiation and Cisplatin.

Secondary Objective(s):

To assess the efficacy of administering weekly Topotecan to patients with carcinoma of the cervix receiving concurrent pelvic radiation and Cisplatin on:

• progression-free survival,
• overall survival, and
• local control

Statistic This is a feasibility study. A two phase accrual will be utilized. If none or 1 of the 6 patients in the first Stage of accrual finish the prescribed therapy in over 8 weeks, then the second Stage of accrual (an additional 6 patients) will increase the Topotecan dose to 3 mg//m2 on days 1, 8, 15, 22, 29 and once during parametrial boost (6 cycles). If 2 or 3 of the patients in the first stage of accrual finish the prescribed therapy in over 8 weeks, the dose of the Topotecan will remain the same in the second Phase of accrual. If 4 or more of the patients in the first stage of accrual finish the prescribed therapy in over 8 weeks, there will be no second phase of accrual.

Conditions

Cervical Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Topotecan

Adding weekly topotecan to cisplatin in patients with primary, locally advanced carcinoma of the cervix receiving pelvic irradiation.

Group Type: EXPERIMENTAL

Topotecan

Intervention Type: DRUG

(First stage of accrual, 6 patients)-2 mg/m2 IV on days 1, 8, 15, 22, 29 and once during parametrial boost (6 cycles)

If none or 1 of the 6 patients in the first Stage of accrual finish the prescribed therapy in over 8 weeks, then the second Stage of accrual (an additional 6 patients) will increase the Topotecan dose to 3 mg/m2 on days 1, 8, 15, 22, 29 and once during parametrical boost (6 cycles). If 2 or 3 of the patients in the first stage of accrual finish the prescribed therapy in over 8 weeks, the dose of the Topotecan will remain the same in the second Phase of accrual. If 4 or more of the patients in the first stage of accrual finish the prescribed therapy in over 8 weeks, there will be no second phase of accrual.

Cisplatin

Intervention Type: DRUG

40 mg/m2 IV (Maximum total dose of 70 mg) on days 1, 8, 15, 22, 29 and once during parametrial boost (6 cycles)

Interventions

Topotecan

(First stage of accrual, 6 patients)-2 mg/m2 IV on days 1, 8, 15, 22, 29 and once during parametrial boost (6 cycles)

If none or 1 of the 6 patients in the first Stage of accrual finish the prescribed therapy in over 8 weeks, then the second Stage of accrual (an additional 6 patients) will increase the Topotecan dose to 3 mg/m2 on days 1, 8, 15, 22, 29 and once during parametrical boost (6 cycles). If 2 or 3 of the patients in the first stage of accrual finish the prescribed therapy in over 8 weeks, the dose of the Topotecan will remain the same in the second Phase of accrual. If 4 or more of the patients in the first stage of accrual finish the prescribed therapy in over 8 weeks, there will be no second phase of accrual.

Intervention Type: DRUG

Cisplatin

40 mg/m2 IV (Maximum total dose of 70 mg) on days 1, 8, 15, 22, 29 and once during parametrial boost (6 cycles)

Intervention Type: DRUG

Other Intervention Names

Hycamtin; Platinol; AQ; NSC #119875

Eligibility Criteria

Inclusion Criteria

1. Patients with primary, previously untreated, histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, Stage I-2, II-B, III-B, IV-A.

2. Patients with negative, non-suspicious para-aortic nodes determined by lymphangiogram, CT, MRI or lymphadenectomy.

3. Patients with adequate bone marrow function: ANC greater than or equal to 1,500/mcl, platelets greater than or equal to 100,000/mcl, and Hemoglobin > 10 mg/dl.

4. Patients with adequate renal function: Creatinine equal to or less than 1.5 mg%.

5. Patients with adequate hepatic function: Bilirubin less than or equal to 1.5 x normal and SGOT and Alkaline phosphatase less than or equal to 3 x normal.

6. Patients who have signed an approved informed consent.

7. Patients with GOG Performance Status of 0, 1, 2, or 3.

8. Patients of childbearing potential must have a negative serum pregnancy test and use an effective form of contraception.

9. Patients who are suitable for treatment with radical intent using concurrent cisplatin and pelvic radiation.

Exclusion Criteria

1. Patients who cannot be or have not been adequately clinically staged.

2. Patients with lower one-third vaginal involvement.

3. Patients with septicemia or severe infection.

4. Patients with circumstances that will not permit completion of the study or required follow-up.

5. Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy.

6. Patients with carcinoma of the cervical stump.

7. Patients who are lactating or pregnant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

University of California, Irvine

OTHER

Sponsor Role: lead

Responsible Party

Chao Family Comprehensive Cancer Center

Cancer Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bradley Monk, MD

Role: PRINCIPAL_INVESTIGATOR

Chao Family Comprehensive Cancer Center

Locations

Chao Family Comprehensive Cancer Center

Orange, California, United States

Countries

United States

References

Gatcliffe TA, Tewari KS, Shah A, Brewster WR, Burger RA, Kuo JV, Monk BJ. A feasibility study of topotecan with standard-dose cisplatin and concurrent primary radiation therapy in locally advanced cervical cancer. Gynecol Oncol. 2009 Jan;112(1):85-9. doi: 10.1016/j.ygyno.2008.09.029. Epub 2008 Nov 1.

Reference Type: RESULT

PMID: 18977518 (View on PubMed)

Other Identifiers

2003-3394

Identifier Type: OTHER

Identifier Source: secondary_id

UCI 03-33

Identifier Type: -

Identifier Source: org_study_id