Topotecan and Gefitinib (Iressa) for Ovarian, Peritoneal, or Fallopian Tube Cancer
A Phase I/II Study of Weekly Topotecan and Gefitinib (Iressa) in Patients With Platinum-Resistant Ovarian, Peritoneal, of Fallopian Tube Cancer
1 other identifier
interventional
19
1 country
1
Brief Summary
The purposes of this study are:
- 1.To determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) weekly of topotecan in combination with standard dose gefitinib in patients with relapsed, platinum-resistant, ovarian, peritoneal or fallopian tube cancers that are epidermal growth factor receptor (EGF-R) positive (\>/= 1+).
- 2.To determine the response rate and response duration in this patient population treated with the maximum tolerated dose (MTD) of topotecan administered on a weekly schedule in combination with standard dose gefitinib, given by way of the mouth (PO) daily.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 ovarian-cancer
Started Sep 2004
Longer than P75 for phase_1 ovarian-cancer
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 2, 2004
CompletedFirst Submitted
Initial submission to the registry
April 21, 2006
CompletedFirst Posted
Study publicly available on registry
April 25, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 4, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 4, 2020
CompletedResults Posted
Study results publicly available
February 7, 2022
CompletedFebruary 7, 2022
January 1, 2022
16.2 years
April 21, 2006
October 25, 2021
January 11, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Dose Limiting Toxicity (DLT)
Dose-limiting toxicity defined as any Grade 4 hematological toxicity and any \> Grade 3 non-hematologic toxicity. The DLT (dose-limiting toxicity) is defined as any Grade 4 hematological toxicity and any \> Grade 3 non-hematologic toxicity.
Continual reassessment method, prior to each 28 day cycle, an average of 60 days
Maximum Tolerated Dose (MTD) of Topotecan
Maximum tolerated dose is highest dose level in which 6 patients treated with at most 1 experiencing DLT.
At end of first course, prior to each new course (28 day cycle). Continual reassessment method (CRM) during each course for toxicity, an average of 60 days
Secondary Outcomes (1)
Response Rate
61 weeks
Study Arms (1)
Topotecan + Gefitinib
EXPERIMENTALPhase I: Topotecan: 2.0, 3.0, or 4.0 mg/m\^2 by vein Days 1, 8 and 15 of 28 day cycle. Gefitinib: 250 mg by mouth daily. Phase II: Topotecan starting dose: MTD from Phase I by vein Days 1, 8, and 15 of 28 day cycle. Gefitinib: 250 by mouth daily for 28 Days.
Interventions
Phase I Starting Dose: 2 mg/m\^2 by vein Weekly Over 30 Minutes on Days 1, 8, and 15. Phase II: MTD dose from Phase I by vein weekly on Days 1, 8, and 15.
Phase I: 250 mg by mouth daily for 28 Days. Phase II: 250 mg by mouth daily for 28 Days.
Eligibility Criteria
You may qualify if:
- Women with platinum-resistant, histologically confirmed epithelial ovarian, fallopian tube or peritoneal cancer. Resistance is defined as: Progression of disease during platinum chemotherapy, or progression of disease within 6 months of completing platinum chemotherapy, or failure to achieve a complete response, with persistent macroscopic disease, after an adequate trial of primary therapy.
- EGF-R expression must be positive (e.g., 1+ or greater) See appendix G.
- Patients with a known hypersensitivity to platinum compounds, who have failed a desensitization regimen, or in the opinion of the investigator, are not good candidates for desensitization, are eligible.
- Patients must have measurable disease.
- Unlimited number of prior chemotherapy regimens are allowed.
- Zubrod performance status \</= 2.
- Patients must have adequate hepatic, renal, and bone marrow function, defined as serum creatinine \</= 2 mg/dl (estimated creatinine clearance 50 ml/min); total bilirubin \< /=2.0 X the upper limit of normal (ULN); alanine aminotransferase (ALT) \</= 2X ULN; white blood count (WBC) \>/= 3,000/mm3; absolute neutrophil count (ANC) \>/= 1,500/mm3; platelets \>/= 100,000/mm3.
- At least three weeks must have elapsed from completion of chemotherapy or radiation therapy.
- At least 30 days must have elapsed from completion of treatment with a non-approved or investigational drug.
- Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with the policies of the hospital. The only approved consent is appended to this protocol.
- Women of childbearing potential must be willing to practice acceptable methods of birth control to prevent pregnancy.
You may not qualify if:
- Patients with borderline or low malignant potential tumors are not eligible.
- Patients who have had prior therapy with topoisomerase I inhibitors.
- Patients who are pregnant or lactating.
- Concurrent chemotherapy, radiation therapy, or surgery (excluding palliative radiation).
- Concurrent, uncontrolled, medical or psychiatric disorders.
- Patients with an active infection.
- Patients with a known hypersensitivity to topotecan or iressa.
- Patients with severe cardiovascular disease (i.e. arrhythmias requiring chronic treatment or congestive heart failure) (NYHA classification III or IV).
- History of other malignancy (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 5 years.
- Patients with overt psychosis or mental disability or otherwise incompetent to give informed consent.
- Patients who have had prior anti-EGFR therapy (i.e. Tarceva, Cetuximab).
- Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.
- Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St. John's Wort.
- Any evidence of clinically active interstitial lung disease (patient with chronic stable radiographic changes who are asymptomatic are eligible).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- AstraZenecacollaborator
- GlaxoSmithKlinecollaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Chelariu-Raicu A, Levenback CF, Slomovitz BM, Wolf J, Bodurka DC, Kavanagh JJ, Morrison C, Gershenson DM, Coleman RL. Phase Ib/II study of weekly topotecan and daily gefitinib in patients with platinum resistant ovarian, peritoneal, or fallopian tube cancer. Int J Gynecol Cancer. 2020 Nov;30(11):1768-1774. doi: 10.1136/ijgc-2020-001863. Epub 2020 Oct 9.
PMID: 33037105DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Diane C Bodurka,Chief Education & Training Ofc, Education & Training
- Organization
- UT MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Charles Levenback, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 21, 2006
First Posted
April 25, 2006
Study Start
September 2, 2004
Primary Completion
November 4, 2020
Study Completion
November 4, 2020
Last Updated
February 7, 2022
Results First Posted
February 7, 2022
Record last verified: 2022-01