Ovarian CancerPhase 2NCT00436644
Lapatinib and Topotecan in Treating Patients With Ovarian Epithelial Cancer or Primary Peritoneal Cancer That Did Not Respond to Cisplatin or Carboplatin
A Phase 2 study testing Lapatinib and Topotecan in people with Ovarian Cancer and Peritoneal Cavity Cancer, run by Mayo Clinic at 3 sites in United States.
Trial summary
RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer, Peritoneal Cavity Cancer
- What is being tested?
- Lapatinib and Topotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2007to Nov 2012
- Phase
- Phase 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed ovarian epithelial or primary peritoneal carcinoma
- Must have one of the following:
- Measurable disease
- Evaluable disease AND a CA-125 value that has increased ≥ 2 times the nadir value established after debulking surgery and first-line chemotherapy, confirmed by a second measurement within the past 21 days
- If a second measurement has not been done, it can be done ≥ 7 days but < 21 days prior to study treatment
- Platinum-refractory and/or -resistant disease after first-line chemotherapy
- Patients retreated with platinum agents (i.e., second relapse) are not eligible
- Patients treated with first-line triplet therapy (e.g., on clinical trial GOG-182) are eligible
- Must have had debulking surgery
- Tissue blocks from this surgery must be available
- No CNS metastases
PATIENT CHARACTERISTICS:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy ≥ 12 weeks
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST ≤ 3 times ULN (5 times ULN if there is liver involvement)
- Creatinine ≤ 1.5 times ULN
- Hemoglobin ≥ 9.0 g/dL
- No uncontrolled infection
- No New York Heart Association class III or IV heart failure
- Left Ventricular Ejection Fraction (LVEF) ≥ 50% by echocardiogram
- No seizure disorder
- No other prior or concurrent malignancy in the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior topotecan hydrochloride
- More than 4 weeks since prior surgery or procedure involving the peritoneum or pleura
- CA125 measurements used as basis for enrollment must be made outside of this 4-week window
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- More than 4 weeks since prior immunotherapy
- More than 4 weeks since prior biologic therapy
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy to > 25 % of bone marrow
- No prior therapy with an anti-epidermal growth factor receptor or anti-HER2 tyrosine kinase inhibitors
- No prior agents targeting topoisomerase I
- No prior or concurrent human anti-mouse antibodies (HAMA) in patients with non-measurable disease
- At least 14 days since prior and no concurrent herbal or dietary supplements
- Vitamin supplements are allowed unless they include herbal additives
- At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the following:
- Rifampin
- Rifabutin
- Rifapentine
- Phenytoin
- Carbamazepine
- Phenobarbital
- Efavirenz
- Nevirapine
- Cortisone (> 50 mg)
- Hydrocortisone (> 40 mg)
- Prednisone (> 10 mg)
- Methylprednisolone (> 8 mg)
- Dexamethasone (> 1.5 mg)
- Oral doses of ≤ 1.6 mg of dexamethasone allowed
- Modafinil
- Hypericum perforatum (St. John's wort)
- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
- Clarithromycin
- Erythromycin
- Troleandomycin
- Itraconazole
- Ketoconazole
- Fluconazole (> 150 mg daily)
- Voriconazole
- Delaviridine
- Nelfinavir
- Amprenavir
- Ritonavir
- Indinavir
- Saquinavir
- Lopinavir
- Verapamil
- Diltiazem
- Nefazodone
- Fluvoxamine
- Cimetidine
- Aprepitant
- Grapefruit or grapefruit juice
- At least 6 months since prior and no concurrent amiodarone
- No concurrent participation in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, gene therapy) for symptom control or therapeutic intent
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Mayo Clinic in Jacksonville
Jacksonville, Florida, 32224
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Mayo Clinic Arizona
Scottsdale, Arizona, 85254
About this study
Official title: A Phase II Trial of Lapatinib in Combination With Weekly Topotecan in Patients With Platinum-Refractory/Resistant Ovarian and Primary Peritoneal Carcinoma
RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with topotecan may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving lapatinib together with topotecan works in treating patients with ovarian epithelial cancer or primary peritoneal cancer that did not respond to cisplatin or carboplatin.
Read the detailed description
OBJECTIVES:
Primary
- Determine the efficacy of lapatinib ditosylate and topotecan hydrochloride, in terms of response, in patients with platinum-resistant or refractory ovarian epithelial or primary peritoneal cavity carcinoma.
Secondary
- Determine the overall survival time in patients treated with this regimen.
- Determine the time to progression in patients treated with this regimen.
- Assess the toxicity profile of this regimen in these patients.
Translational
- Determine the expression patterns of epidermal growth factor receptor, HER2/neu, hypoxia-induced factor 1 alpha, CD31, breast cancer resistance protein, and topoisomerase I by immunohistochemistry using tumor tissue from primary debulking surgery.
- Determine the feasibility of monitoring circulating tumor cells with specific biological markers to determine or follow response in these patients.
OUTLINE: This is a multicenter study.
Patients receive oral lapatinib ditosylate once daily on days 1-28 and topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and on day 8 of course 1 (immediately after the topotecan infusion) and are evaluated for pharmacological studies. Tumor tissue samples obtained at debulking surgery are examined by immunohistochemistry for epidermal growth factor receptor, HER1, ErbB1, HER2/neu, ErbB2, hypoxia-induced factor 1 alpha, CD31, platelet endothelial cell adhesion molecule 1, topoisomerase I, and breast cancer resistance protein.
After the completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.
- Conditions
- Ovarian Cancer, Peritoneal Cavity Cancer
- Being tested
- Lapatinib, Topotecan
- Keywords
- recurrent ovarian epithelial cancer, peritoneal cavity cancer
- Medical subject headings
- Ovarian Neoplasms, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LapatinibDrug
Also called Tykerb
1250 mg orally days 1 -28.
TopotecanDrug
Also called Hycamptin
3.2 mg/m2 IV over 30 min in 100mL D5W (5% dextrose in water) or 0.9% NS at days 1, 8 \& 15.
| Study group | Role | What they receive |
|---|---|---|
| Lapatinib + Topotecan | Experimental | Assess biological effects of topotecan and lapatinib in patients with epithelial ovarian cancer and primary peritoneal carcinoma. Receives: Drug: Lapatinib; Drug: Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (Complete Response (CR) or Partial Response (PR))
Measurable disease patients: measureable disease is defined as at least one lesion whose longest diameter >= 2cm with conventional techniques or >=1cm with spiral CT
- Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 4 weeks apart.
- Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions.
Non-measurable disease patients:
- Decrement in CA125 by > 50%
- Improvement in other evaluable disease
Measured: Two consecutive evaluations at least 4 weeks apart
Secondary outcomes (3)
Time to Progression
Time to progression was defined as the number of months from registration to the date of disease progression, with patients who are progression free being censored on the date of their last evaluation.
Measured: Time from registration to progression (up to 2 years)
Adverse Event Profile
Number of patients that experienced adverse events (grade 3 or more) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0
Measured: Every 4 weeks
Overall Survival
Overall survival time was defined as the number of months from registration to the date of death or last follow-up
Measured: Time from Registration to Death or last follow-up (up to 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2007 (estimated)
- Study startMar 2007
- Primary completionMar 2009
- Study completionNov 2012
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.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Paul Haluska, MD, PhD, Study chair, Mayo ClinicJohn K. Camoriano, M.D., Principal investigator, Mayo ClinicCandido E. Rivera, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00436644
- Sponsor's protocol ID
- RC0661
- Other IDs
- P30CA015083, RC0661, 06-002426
- Status last verified
- Mar 2014
- First submitted
- 15 Feb 2007
- Last updated
- 16 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Lapatinib in Combination With Weekly Topotecan in Patients With Platinum-Refractory/Resistant Ovarian and Primary Peritoneal Carcinoma
- ClinicalTrials.gov ID
- NCT00436644
- Acronym / sponsor ID
- RC0661
- Conditions
- Ovarian Cancer, Peritoneal Cavity Cancer
- Keywords
- recurrent ovarian epithelial cancer, peritoneal cavity cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 19 Feb 2007 (estimated)
- Results
- Posted 22 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with topotecan may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving lapatinib together with topotecan works in treating patients with ovarian epithelial cancer or primary peritoneal cancer that did not respond to cisplatin or carboplatin.
Detailed description
OBJECTIVES:
Primary
- Determine the efficacy of lapatinib ditosylate and topotecan hydrochloride, in terms of response, in patients with platinum-resistant or refractory ovarian epithelial or primary peritoneal cavity carcinoma.
Secondary
- Determine the overall survival time in patients treated with this regimen.
- Determine the time to progression in patients treated with this regimen.
- Assess the toxicity profile of this regimen in these patients.
Translational
- Determine the expression patterns of epidermal growth factor receptor, HER2/neu, hypoxia-induced factor 1 alpha, CD31, breast cancer resistance protein, and topoisomerase I by immunohistochemistry using tumor tissue from primary debulking surgery.
- Determine the feasibility of monitoring circulating tumor cells with specific biological markers to determine or follow response in these patients.
OUTLINE: This is a multicenter study.
Patients receive oral lapatinib ditosylate once daily on days 1-28 and topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and on day 8 of course 1 (immediately after the topotecan infusion) and are evaluated for pharmacological studies. Tumor tissue samples obtained at debulking surgery are examined by immunohistochemistry for epidermal growth factor receptor, HER1, ErbB1, HER2/neu, ErbB2, hypoxia-induced factor 1 alpha, CD31, platelet endothelial cell adhesion molecule 1, topoisomerase I, and breast cancer resistance protein.
After the completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lapatinib + Topotecan | Experimental | Drug: Lapatinib, Drug: TopotecanAssess biological effects of topotecan and lapatinib in patients with epithelial ovarian cancer and primary peritoneal carcinoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| LapatinibAlso: Tykerb1250 mg orally days 1 -28. | Drug | Lapatinib + Topotecan |
| TopotecanAlso: Hycamptin3.2 mg/m2 IV over 30 min in 100mL D5W (5% dextrose in water) or 0.9% NS at days 1, 8 \& 15. | Drug | Lapatinib + Topotecan |
Primary outcome
Response Rate (Complete Response (CR) or Partial Response (PR))
Time frame: Two consecutive evaluations at least 4 weeks apart
Measurable disease patients: measureable disease is defined as at least one lesion whose longest diameter >= 2cm with conventional techniques or >=1cm with spiral CT * Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 4 weeks apart. * Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions. Non-measurable disease patients: * Decrement in CA125 by > 50% * Improvement in other evaluable disease
3 secondary outcomes
Time to Progression
Time frame: Time from registration to progression (up to 2 years)
Adverse Event Profile
Time frame: Every 4 weeks
Overall Survival
Time frame: Time from Registration to Death or last follow-up (up to 3 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Paul Haluska, MD, PhD study chair
Mayo Clinic
John K. Camoriano, M.D. principal investigator
Mayo Clinic
Candido E. Rivera, M.D. principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lapatinib and Topotecan in people with Ovarian Cancer and Peritoneal Cavity Cancer, run by Mayo Clinic at 3 sites 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?
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 16 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 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 22 Mar 2012). 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?
Response Rate (Complete Response (CR) or Partial Response (PR)) (time frame: Two consecutive evaluations at least 4 weeks apart). 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 16 Apr 2014.