Ovarian CancerPhase 1/2NCT00317772
Topotecan and Gefitinib (Iressa) for Ovarian, Peritoneal, or Fallopian Tube Cancer
A Phase 1/2 study testing Topotecan and Gefitinib in people with Ovarian Cancer and Peritoneal Neoplasms, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Ovarian Cancer, Peritoneal Neoplasms, Fallopian Tube Cancer
- What is being tested?
- Topotecan and Gefitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2004to 4 Nov 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase I/II Study of Weekly Topotecan and Gefitinib (Iressa) in Patients With Platinum-Resistant Ovarian, Peritoneal, of Fallopian Tube Cancer
The purposes of this study are:
- 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+).
- 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.
Read the detailed description
Gefitinib inhibits the activity of a molecule present on the cancer cell that plays a role in cancer cell growth. Topotecan is an FDA approved drug used to treat ovarian cancer that is still present after treatment with chemotherapy. It is also used to treat recurrent ovarian cancer (patients whose cancer returns after they have been cancer-free for a period of time).
Before treatment starts, you will have a complete physical exam, routine blood tests (about 2-3 teaspoons), a chest x-ray, and a CT scan or MRI. Women who are able to have children must have a negative blood pregnancy test.
There are 2 phases to this study. In the first phase, 3 different dose levels of topotecan are being studied. The dose of topotecan that you receive will depend on when you are enrolled. It will also depend on whether or not other participants had side effects from their treatment. Although the dose of topotecan will vary, the dose of gefitinib is the same for all participants. Up to 6 participants may be treated at each dose. The goal of this portion of the study is to find the highest safe dose of this drug combination. Up to 18 patients will be treated on this part of the study.
Once the highest safe dose of topotecan has been found, the second phase of the study will begin. In this phase, all participants will receive the same dose of topotecan and gefitinib. Up to 40 patients will be enrolled in this part of the study (but 6 will be from the 1st portion of the study.
Each treatment cycle is 28 days long. You will take one gefitinib tablet by mouth every day beginning on Day 1. In addition, you will be given topotecan through a catheter (tube) placed in a vein over 30 minutes on Days 1, 8, and 15.
Blood tests to check your kidney, liver, and bone marrow function and a complete checkup (physical examination, including a pelvic and rectal exam) will be done before each course of therapy and a month after treatment ends. About 2-3 teaspoons of blood will be collected for routine blood tests each time blood is drawn during this study. Follow up CT scans or MRI scans will be done after every 2 to 3 cycles to evaluate your response to treatment.
You will be taken off study if your disease gets worse or intolerable side effects occur. If you have a complete response to this therapy (no evidence of cancer) then treatment will continue for an additional 6 months and then stop. All treatment is given on an outpatient basis at UTMDACC.
You will be monitored for at least 30 days after your last dose of therapy. If you have side effects related to this treatment combination, you will be monitored longer (until the side effects have gone away).
This is an investigational study. Both gefitinib and topotecan are FDA approved and commercially available. However, their use together in this study is investigational. A total of up to 52 patients will take part in this study. All will be enrolled at UTMDACC.
- Conditions
- Ovarian Cancer, Peritoneal Neoplasms, Fallopian Tube Cancer
- Keywords
- Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer, Epidermal Growth Factor, Platinum Hypersensitivity, Hycamtin, Gefitinib, Iressa, Topotecan, EGFR
- Medical subject headings
- Ovarian Neoplasms, Peritoneal Neoplasms, Fallopian Tube Neoplasms, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopotecanDrug
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.
GefitinibDrug
Also called Iressa
Phase I: 250 mg by mouth daily for 28 Days.
Phase II: 250 mg by mouth daily for 28 Days.
| Study group | Role | What they receive |
|---|---|---|
| Topotecan + Gefitinib | Experimental | Phase 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. Receives: Drug: Topotecan; Drug: Gefitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension. Complete Response (CR): disappearance of all target and non-target lesions and no evidence of new lesions. Partial Response (PR): At least 30% decrease in sum of longest dimensions (LD) of all target measurable lesions. Increasing Disease: At least a 20% increase in sum of LD of target lesions taking as reference smallest sum LD or appearance of new lesions within 8 weeks of study entry. Progression on existing non-target lesions, other than pleural effusions without cytological proof of neoplastic origin. Death due to disease without prior objective documentation of progression. Global deterioration in health status attributable to disease requiring a change in therapy without objective evidence of progression.
Measured: 61 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2006 (estimated)
- Study start2 Sep 2004
- Primary completion4 Nov 2020
- Study completion4 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Charles Levenback, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00317772
- Sponsor's protocol ID
- 2003-0322
- Status last verified
- Jan 2022
- First submitted
- 21 Apr 2006
- Last updated
- 7 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33037105
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Weekly Topotecan and Gefitinib (Iressa) in Patients With Platinum-Resistant Ovarian, Peritoneal, of Fallopian Tube Cancer
- ClinicalTrials.gov ID
- NCT00317772
- Acronym / sponsor ID
- 2003-0322
- Conditions
- Ovarian Cancer, Peritoneal Neoplasms, Fallopian Tube Cancer
- Keywords
- Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer, Epidermal Growth Factor, Platinum Hypersensitivity, Hycamtin, Gefitinib, Iressa
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- AstraZeneca, GlaxoSmithKline
- Study start
- 2 Sep 2004 (actual)
- Primary completion
- 4 Nov 2020 (actual)
- Study completion
- 4 Nov 2020 (actual)
- First posted
- 25 Apr 2006 (estimated)
- Results
- Posted 7 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purposes of this study are:
- 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+).
- 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.
Detailed description
Gefitinib inhibits the activity of a molecule present on the cancer cell that plays a role in cancer cell growth. Topotecan is an FDA approved drug used to treat ovarian cancer that is still present after treatment with chemotherapy. It is also used to treat recurrent ovarian cancer (patients whose cancer returns after they have been cancer-free for a period of time).
Before treatment starts, you will have a complete physical exam, routine blood tests (about 2-3 teaspoons), a chest x-ray, and a CT scan or MRI. Women who are able to have children must have a negative blood pregnancy test.
There are 2 phases to this study. In the first phase, 3 different dose levels of topotecan are being studied. The dose of topotecan that you receive will depend on when you are enrolled. It will also depend on whether or not other participants had side effects from their treatment. Although the dose of topotecan will vary, the dose of gefitinib is the same for all participants. Up to 6 participants may be treated at each dose. The goal of this portion of the study is to find the highest safe dose of this drug combination. Up to 18 patients will be treated on this part of the study.
Once the highest safe dose of topotecan has been found, the second phase of the study will begin. In this phase, all participants will receive the same dose of topotecan and gefitinib. Up to 40 patients will be enrolled in this part of the study (but 6 will be from the 1st portion of the study.
Each treatment cycle is 28 days long. You will take one gefitinib tablet by mouth every day beginning on Day 1. In addition, you will be given topotecan through a catheter (tube) placed in a vein over 30 minutes on Days 1, 8, and 15.
Blood tests to check your kidney, liver, and bone marrow function and a complete checkup (physical examination, including a pelvic and rectal exam) will be done before each course of therapy and a month after treatment ends. About 2-3 teaspoons of blood will be collected for routine blood tests each time blood is drawn during this study. Follow up CT scans or MRI scans will be done after every 2 to 3 cycles to evaluate your response to treatment.
You will be taken off study if your disease gets worse or intolerable side effects occur. If you have a complete response to this therapy (no evidence of cancer) then treatment will continue for an additional 6 months and then stop. All treatment is given on an outpatient basis at UTMDACC.
You will be monitored for at least 30 days after your last dose of therapy. If you have side effects related to this treatment combination, you will be monitored longer (until the side effects have gone away).
This is an investigational study. Both gefitinib and topotecan are FDA approved and commercially available. However, their use together in this study is investigational. A total of up to 52 patients will take part in this study. All will be enrolled at UTMDACC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Topotecan + Gefitinib | Experimental | Drug: Topotecan, Drug: GefitinibPhase 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. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TopotecanPhase 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. | Drug | Topotecan + Gefitinib |
| GefitinibAlso: IressaPhase I: 250 mg by mouth daily for 28 Days. Phase II: 250 mg by mouth daily for 28 Days. | Drug | Topotecan + Gefitinib |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: Continual reassessment method, prior to each 28 day cycle, an average of 60 days
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.
Maximum Tolerated Dose (MTD) of Topotecan
Time frame: 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
Maximum tolerated dose is highest dose level in which 6 patients treated with at most 1 experiencing DLT.
1 secondary outcome
Response Rate
Time frame: 61 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33037105Chelariu-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.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Levenback, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Topotecan and Gefitinib in people with Ovarian Cancer and Peritoneal Neoplasms, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) (time frame: Continual reassessment method, prior to each 28 day cycle, an average of 60 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00317772, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2022.