Rectal NeoplasmsPhase 1NCT00215956
A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Carcinoma
A Phase 1 study testing topotecan, radiation and surgery in people with Rectal Neoplasms, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
This is an open-label, single center, phase I study designed to determine the MTD or oral topotecan as a radiosensitizing agent in the treatment of rectal cancer patients. Sequential cohorts of three patients will be given increasing doses of oral topotecan and fixed doses of concurrent radiation (45GY) over five… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Neoplasms
- What is being tested?
- topotecan, radiation and surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2001to Jan 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically confirmed rectal cancer.
- Written Informed Consent
- Patients should be a candidate for preoperative radiotherapy
- A primary tumor of 3cm or greater with a clinical stage of T2, T3 or T4 and any N according to the Astler-Coller modification of the Dukes staging system
- Patient must be 18 years of age or older
- Must have an ECOG performance status of 2 or Less
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- Diagnosis of rectal cancer should be no more than 90 days from initial clinic visit or from the start of therapy
- Patients must be seen and evaluated at the H. Lee Moffitt Cancer Center
- Patients must be recovered from prior surgery
- Patients must have a life expectancy of 3 months or greater
- Laboratory criteria: WBC of 3,500/mm3 or greater; Neutrophils of 1,500mm3 or greater; Platelet count of 100,000/mm3 or greater; Serum creatinine of 1.5 mg/dl or lesser; or creatinine clearance of greater than 60ml/min; SGOT/AST \& SGPT/ALT \& alkaline phosphatase of 2 times or lesser than the upper limit or normal if liver metastases are present; Serum bilirubin of 1.5mg/dl or lesser.
Who cannot join
- Patients with their primary tumor totally excised at time of diagnosis
- Patients with recurrent rectal cancer that failed initial treatment
- Patients previously treated with topotecan
- Patients with active infection
- Any known primary or secondary immunodeficiencies
- Any condition of the GI tract which would affect GI absorption or motility (e.g., autonomic neuropathy, active gastric or duodenal ulcers or certain gastrointestinal surgeries). Patients receiving medication to maintain motility or gastric emptying are also excluded.
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- Patients with uncontrolled emesis, regardless of etiology.
- Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or a low grade prostate cancer.
- Concurrent severe medical problems unrelated to the malignancy which would significantly limit full compliance with the study or expose the patient to significant risk.
- Patients of child bearing potential, not practicing adequate contraception (barrier method or IUD for three months before the start of the study an agree to continue for at least 4 weeks after the end of the study)
- Patients who are pregnant or lactating
- Use of an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
This is an open-label, single center, phase I study designed to determine the MTD or oral topotecan as a radiosensitizing agent in the treatment of rectal cancer patients. Sequential cohorts of three patients will be given increasing doses of oral topotecan and fixed doses of concurrent radiation (45GY) over five weeks.
Read the detailed description
This is an open-label, single center, phase I study designed to determine the MTD or oral topotecan as a radiosensitizing agent in the treatment of rectal cancer patients. Sequential cohorts of three patients will be given increasing doses of oral topotecan and fixed doses of concurrent radiation (45GY) over five weeks. The starting dose of oral topotecan is 0.25mg/m2 to be concomitantly administered with radiation (45Gy) x 5 days every week unless the radiation is interrupted for Holidays/Weekends or toxicity requiring treatment delays occurs.
A total of 25 doses is planned. Doses will be escalated in 0.15 mg/m2 increments thereafter in subsequent cohorts. Topotecan will be administered immediately before daily radiation.
All patients will undergo a rectal biopsy before treatment begins and during treatment. Tissue will be submitted to H. Lee Moffitt Cancer Center for tumor marker assays. Tissue from the excised tumor at the time of surgery will also be sent for the same studies. Between day 10 and 14 of treatment, colonoscopy/sigmoidoscopy is mandatory to ensure having a quantitative estimate of the tumor shrinkage and to obtain a repeat rectal biopsy. All patients will undergo radiation therapy concurrently with oral topotecan. Patients will receive 180 cGY per fraction to a total dose of 4500cGy(conventional fractionation) to the pelvis using a 3 or 4 filed technique and high energy photons. Standardized fields for rectal cancer will be used to include the true pelvis (mid sacrum to at least 2-3 centimeters below the inferior aspect of the tumor volume).
Patients will undergo surgery-either a low anterior resection, abdominoperineal resection or local excision. All patients will be offered postoperative adjuvant chemotherapy consisting of 5-Fluorouracil (F-FU) 350 mg/m2/day i.v. for 5 days administered every 28 days times four cycles. Immediately prior to the administration of 5-FU, leucovorin will be administered at a dose of 20 mg/m2/day i.v. push daily for 5 days every 28 days times four cycles.
- Conditions
- Rectal Neoplasms
- Keywords
- Topotecan, Rectal Neoplasms, Radiosensitizing
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
topotecanDrug
Preoperative treatment: oral topotecan 5 days per week for up to 5 weeks
radiationProcedure or surgery
Preoperative radiation
surgeryProcedure or surgery
surgery to remove tumor 4 to 8 weeks following completion of preoperative treatment
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation and Radiation, Followed by Surgery | Experimental | Preoperative treatment with radiation and oral topotecan for up to 5 weeks, followed by surgery. Receives: Drug: topotecan; Procedure: radiation; Procedure: surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Topotecan
Dose escalation to determine MTD that can be given with radiation.
Measured: up to 5 weeks
Side Effect Profile of Topotecan
Review of adverse events
Measured: Up to 5 weeks
Secondary outcomes (1)
Response Rate
To determine pathologic response to treatment and assessment of sphincter preservation.
Measured: Up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startNov 2001
- Primary completionJan 2008
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- William Dinwoodie, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00215956
- Sponsor's protocol ID
- MCC-12349
- Other IDs
- USFIRB#5881
- Status last verified
- Jan 2009
- First submitted
- 19 Sep 2005
- Last updated
- 23 Dec 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Carcinoma
- ClinicalTrials.gov ID
- NCT00215956
- Acronym / sponsor ID
- MCC-12349
- Conditions
- Rectal Neoplasms
- Keywords
- Topotecan, Rectal Neoplasms, Radiosensitizing
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Nov 2001
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, single center, phase I study designed to determine the MTD or oral topotecan as a radiosensitizing agent in the treatment of rectal cancer patients. Sequential cohorts of three patients will be given increasing doses of oral topotecan and fixed doses of concurrent radiation (45GY) over five weeks.
Detailed description
This is an open-label, single center, phase I study designed to determine the MTD or oral topotecan as a radiosensitizing agent in the treatment of rectal cancer patients. Sequential cohorts of three patients will be given increasing doses of oral topotecan and fixed doses of concurrent radiation (45GY) over five weeks. The starting dose of oral topotecan is 0.25mg/m2 to be concomitantly administered with radiation (45Gy) x 5 days every week unless the radiation is interrupted for Holidays/Weekends or toxicity requiring treatment delays occurs.
A total of 25 doses is planned. Doses will be escalated in 0.15 mg/m2 increments thereafter in subsequent cohorts. Topotecan will be administered immediately before daily radiation.
All patients will undergo a rectal biopsy before treatment begins and during treatment. Tissue will be submitted to H. Lee Moffitt Cancer Center for tumor marker assays. Tissue from the excised tumor at the time of surgery will also be sent for the same studies. Between day 10 and 14 of treatment, colonoscopy/sigmoidoscopy is mandatory to ensure having a quantitative estimate of the tumor shrinkage and to obtain a repeat rectal biopsy. All patients will undergo radiation therapy concurrently with oral topotecan. Patients will receive 180 cGY per fraction to a total dose of 4500cGy(conventional fractionation) to the pelvis using a 3 or 4 filed technique and high energy photons. Standardized fields for rectal cancer will be used to include the true pelvis (mid sacrum to at least 2-3 centimeters below the inferior aspect of the tumor volume).
Patients will undergo surgery-either a low anterior resection, abdominoperineal resection or local excision. All patients will be offered postoperative adjuvant chemotherapy consisting of 5-Fluorouracil (F-FU) 350 mg/m2/day i.v. for 5 days administered every 28 days times four cycles. Immediately prior to the administration of 5-FU, leucovorin will be administered at a dose of 20 mg/m2/day i.v. push daily for 5 days every 28 days times four cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and Radiation, Followed by Surgery | Experimental | Drug: topotecan, Procedure: radiation, Procedure: surgeryPreoperative treatment with radiation and oral topotecan for up to 5 weeks, followed by surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with histologically confirmed rectal cancer.
- Written Informed Consent
- Patients should be a candidate for preoperative radiotherapy
- A primary tumor of 3cm or greater with a clinical stage of T2, T3 or T4 and any N according to the Astler-Coller modification of the Dukes staging system
- Patient must be 18 years of age or older
Key exclusion criteria (12 listed)
- Patients with their primary tumor totally excised at time of diagnosis
- Patients with recurrent rectal cancer that failed initial treatment
- Patients previously treated with topotecan
- Patients with active infection
- Any known primary or secondary immunodeficiencies
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 |
|---|---|---|
| topotecanPreoperative treatment: oral topotecan 5 days per week for up to 5 weeks | Drug | Dose Escalation and Radiation, Followed by Surgery |
| radiationPreoperative radiation | Procedure or surgery | Dose Escalation and Radiation, Followed by Surgery |
| surgerysurgery to remove tumor 4 to 8 weeks following completion of preoperative treatment | Procedure or surgery | Dose Escalation and Radiation, Followed by Surgery |
Primary outcome
Maximum Tolerated Dose (MTD) of Topotecan
Time frame: up to 5 weeks
Dose escalation to determine MTD that can be given with radiation.
Side Effect Profile of Topotecan
Time frame: Up to 5 weeks
Review of adverse events
1 secondary outcome
Response Rate
Time frame: Up to 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2013.
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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.
William Dinwoodie, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing topotecan, radiation and surgery in people with Rectal Neoplasms, run by H. Lee Moffitt Cancer Center and Research Institute 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 12 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 23 Dec 2013. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Tolerated Dose (MTD) of Topotecan (time frame: up to 5 weeks). 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?
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 23 Dec 2013.