Ductal Carcinoma in SituPhase 1/2NCT01372618
Breast Cancer Chemoprevention by SOM230, an IGF-I Action Inhibitor
A Phase 1/2 study testing SOM 230 / Pasireotide in people with Ductal Carcinoma in Situ, run by NYU Langone Health at 1 site in United States.
Trial summary
This will be a proof of principle clinical trial to evaluate the use of pasireotide (SOM230) in women with ductal carcinoma in situ (DCIS) of the breast. Surgery and radiotherapy are used as treatment for DCIS and subsequent treatment with antiestrogens has been effective in reducing the occurrence of invasive breast… Read more about this study
- Who is it for?
- Ages 21 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Ductal Carcinoma in Situ
- What is being tested?
- SOM 230 / Pasireotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to Oct 2015
- 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 21 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 21 years of age and older
- Must sign informed consent, witnessed, and dated prior to entry
- The participant has breast biopsy consistent with Ductal Carcinoma in situ (DCIS)
- Performance Status: ECOG 0-1 unless mobility is limited from chronic physical handicap
- No clinical evidence of other malignancies (except Basal Cell carcinoma)
- Complete blood count, differential and platelet count must be WNL or verified by the study chair to be related to conditions not interfering with normal health status
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- Adequate hepatic and renal function (these must be WNL or verified by study chair to be related to conditions not interfering with normal health status)
- Normal fasting glucose
- No history of diabetes
- Medically and Psychologically able to comply with all study requirements
- Accessible for Follow up
Who cannot join
- Less than 21 years of age
- Known invasive breast cancer of any type
- Bilateral prophylactic mastectomy
- Prior malignancy of any type that occurred less than 5 years previously, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- Existing non-malignant disease that would preclude the administration of pasireotide
- Pregnancy: All subjects will have a beta-hCG serum pregnancy test to rule out pregnancy, a history will also be taken to make certain that recent sexual exposure does not put them at risk for pregnancy. If so a second serum pregnancy test will be done. Volunteers will be asked to use barrier contraception during study.
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- Tamoxifen or other preventive measures within 6 months
- Serious Psychiatric condition or addictive disorder
- Diabetes or elevated fasting blood sugar either by history or by HgbA1c greater than 6.5% or fasting serum glucose greater than 100mg/dL on screening labs. If fasting serum glucose is greater than 100mg/dL on screening labs, this test will be repeated to confirm the results
- Inability to inject medication or test for finger stick glucose
- Gall bladder disease
- History of cholecystitis without cholecystectomy
- Electrolyte abnormalities (particularly hypokalemia or hypomagnesemia)
- Contraindication for MRI
- If tumor size is < 1cm on mammography and all calcifications are removed on core biopsy the patient will be excluded.
- QT related exclusion criteria
- QTcF at screening > 450 msec.
- History of syncope or family history of idiopathic sudden death.
- Sustained or clinically significant cardiac arrhythmias.
- Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block.
- Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
- Concomitant medication(s) known to increase the QT interval.
- Hepatic Related Exclusion Criteria
- Baseline Alanine transaminase (ALT) or Aspartate transaminase (AST) > 2x upper limit of normal (ULN) without known complications of metastatic liver disease or primary hepatic disease (e.g. Cushing's disease and Acromegaly studies).
- Baseline Total Bilirubin > 1.5x ULN
Trial locations and contacts
1 site in 1 country.
About this study
This will be a proof of principle clinical trial to evaluate the use of pasireotide (SOM230) in women with ductal carcinoma in situ (DCIS) of the breast. Surgery and radiotherapy are used as treatment for DCIS and subsequent treatment with antiestrogens has been effective in reducing the occurrence of invasive breast cancer. Unfortunately, treatment with antiestrogens carries potential serious side effects and toxicities that are intolerable to some patients. Preliminary data suggest that inhibition of IGF-1 action in the breast will be at least as effective as tamoxifen. Pasireotide is a somatostatin analog that prevents mammary development by inhibiting IGF-1 action directly in the mammary gland and also indirectly without causing menopausal symptoms. This study is an expansion of work that we have previously done in women with atypical hyperplasia of the breast, which showed that treatment with pasireotide for 10 days caused a reduction in the cellularity of these precancerous lesions. In our present study, women with DCIS will be treated with pasireotide for 20 days prior to surgical excision. Endpoints will be as follows:
- To determine whether pasireotide will inhibit cell proliferation and angiogenesis (signs of tumor growth), and stimulate apoptosis (cell death) in surgically excised tissue in comparison to core biopsies from women with estrogen receptor (ER) positive DCIS. Both the core biopsy and surgical excision are standard of care procedures that women with DCIS have regardless of participation in this trial.
- To use dynamic contrast enhanced MRI to assess patients before and after treatment with pasireotide and evaluate for changes in tumor volume and other tumor related features
- In our previous study we found that many women experienced a slight elevation in blood sugar with 10 days of treatment with pasireotide. Other work has shown that this effect often resolves with greater duration of treatment. We are therefore expanding the duration of treatment in this study to 20 days to assess if the initial hyperglycemia seen with pasireotide improves as treatment duration progresses.
Read the detailed description
Ductal carcinoma in situ (DCIS) is a direct precursor of invasive breast cancer and is also a marker of an increased chance of developing invasive cancer in the ipsilateral and contralateral breast. Surgery and radiotherapy are used as treatment for DCIS and subsequent treatment with antiestrogens has been effective in reducing the occurrence of invasive breast cancer in DCIS patients. Unfortunately, treatment with antiestrogens carries potential side effects and toxicities. The investigators have data to suggest that inhibition of IGF-I action in the breast will be more effective than antiestrogens, raising hopes it might be effective enough to stand alone as a treatment. Pasireotide is a somatostatin analog that prevents mammary development by inhibiting IGF-I action directly in the mammary gland and also indirectly, without causing menopausal symptoms and signs. As both estrogen (E2) and progesterone (P) require IGF-I in order to act, part of the inhibitory effect of pasireotide is on prevention of estrogen action. The investigators have data that indicate that IGF-I also has direct actions on the breast that are independent of steroid hormones. One example is that IGF-I has a direct stimulatory effect on mammary development in the absence of E2. Additionally, IGF-I has effects on ER-negative tumor cell lines that can be reversed by IGF-I inhibition. If pasireotide inhibited both E2 related and E2 unrelated effects of IGF-I it would likely be more effective than antiestrogens. Preliminary data in rats show that pasireotide, at minimum, can entirely substitute for tamoxifen. To determine whether pasireotide had activities in women at high risk for breast cancer, similar to those observed in rats, the investigators were awarded a DOD Synergistic Idea grant. Those data are expected to be reported soon.
The investigators plan to expand this work to determine in principle whether pasireotide has the potential to treat DCIS. The investigators plan on treating 24 women, with low grade (8), intermediate grade (8) and high grade (8) ER-positive DCIS tumors. The investigators will assess its effect on apoptosis, cell proliferation, angiogenesis, ER and PR and phosphorylation of IGF-IR and IRS-1 before and after 20 days of treatment with pasireotide in core biopsy vs. surgical excision specimens. These endpoints will be measured by specific immunohistochemistry. Simultaneously, the investigators will determine whether IGF-I inhibition will reduce angiogenesis in DCIS using dynamic contrast enhanced MRI (DCE-MRI) at 3.0 Tesla, in addition to mammography. This MRI technique is able to detect early changes of neo-angiogenesis associated with invasive breast cancers and DCIS. Pasireotide should theoretically inhibit angiogenesis in these women, as it does in mice. The DCE-MRI may also show changes in tumor volume, morphologic and kinetic features. Imaging will serve as an additional measure to monitor response to treatment. Results will be correlated with pathology and immunohistochemical endpoints.
In our previous work the investigators noted that there was an increase in blood glucose early after starting pasireotide, but the work of others has indicated that this side effect lasts only several weeks. The investigators found that suppressed levels of insulin (due to pasireotide effect on β cells) began to rise by day 10 of treatment. Therefore, extending the treatment period from 10 to 20 days with daily monitoring of patients will enable us to make certain that the early elevated glucose associated with pasireotide is only temporary. Another side effect is reduction in circulating levels of IGF-I. Theoretically, this could lead to body changes associated with growth hormone deficiency (GHD). Although, tamoxifen and raloxifene also lower serum IGF-I, and women taking it do not usually complain of symptoms of GHD, this is an issue that must be further investigated. However, if pasireotide is found to be effective in the treatment of DCIS, the benefit would likely outweigh the risk.
- Conditions
- Ductal Carcinoma in Situ
- Being tested
- SOM 230 / Pasireotide
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SOM 230 / PasireotideDrug
SOM230/Pasireotide is a multi-receptor targeted somatostatin analogue. In this trial, 600 mcg of SOM230/Pasireotide are taken twice daily subcutaneously.
| Study group | Role | What they receive |
|---|---|---|
| SOM 230/Pasireotide | Experimental | Treatment with SOM230 600mcg twice daily for 20 days. Receives: Drug: SOM 230 / Pasireotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cell Proliferation and Apoptosis
Tissue from initial diagnostic breast biopsies will be compared to the remaining tissue excised after treatment with SOM230. Tissue will be stained to measure cell proliferation and apoptosis (cell death).
Measured: Before and after 20 days of treatment
Secondary outcomes (2)
Effect of SOM 230 / Pasireotide on Tumor Volume and Tumor Kinetics
To determine whether pasireotide prevents angiogenesis in DCIS as it does in the rat mammary gland, we will immunostain tissue samples for Factor VIII to identify vessels in DCIS before and after treatment. Further, using dynamic contrast enhanced MRI (DCE-MRI) we plan to detect changes in angiogenesis in vivo, non-invasively, and also detect effects of pasireotide which theoretically should inhibit vascularity. We propose to evaluate changes in the size of the lesion, changes in the morphologic appearance and kinetic features of the lesion.
Measured: Before and after 20 days of treatment
Hyperglycemia
In our previous study, we found that women had moderately increased blood sugar early after starting SOM230. In other studies in normal individuals this effect disappeared by a week or two. We found some evidence of improvement during administration. However, extending the treatment period from 9.5 to 19.5 days will enable us to make certain that the early elevated sugar associated with SOM230 is only temporary.
Measured: Before and after 20 days of treatment with 3 month post-treatment follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionOct 2015
- Study completionOct 2015
Why it stopped: PI has passed away. Requested by department to terminate study.
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 Ductal Carcinoma in SituStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David L Kleinberg, MD, Principal investigator, NYU School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01372618
- Sponsor's protocol ID
- 10-00641
- Other IDs
- BC097854
- Status last verified
- Nov 2017
- First submitted
- 9 Jun 2011
- Last updated
- 27 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Breast Cancer Chemoprevention by SOM230, an IGF-I Action Inhibitor
- ClinicalTrials.gov ID
- NCT01372618
- Acronym / sponsor ID
- 10-00641
- Conditions
- Ductal Carcinoma in Situ
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI has passed away. Requested by department to terminate study.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Jun 2011 (actual)
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 14 Jun 2011 (estimated)
- Results
- Posted 27 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a proof of principle clinical trial to evaluate the use of pasireotide (SOM230) in women with ductal carcinoma in situ (DCIS) of the breast. Surgery and radiotherapy are used as treatment for DCIS and subsequent treatment with antiestrogens has been effective in reducing the occurrence of invasive breast cancer. Unfortunately, treatment with antiestrogens carries potential serious side effects and toxicities that are intolerable to some patients. Preliminary data suggest that inhibition of IGF-1 action in the breast will be at least as effective as tamoxifen. Pasireotide is a somatostatin analog that prevents mammary development by inhibiting IGF-1 action directly in the mammary gland and also indirectly without causing menopausal symptoms. This study is an expansion of work that we have previously done in women with atypical hyperplasia of the breast, which showed that treatment with pasireotide for 10 days caused a reduction in the cellularity of these precancerous lesions. In our present study, women with DCIS will be treated with pasireotide for 20 days prior to surgical excision. Endpoints will be as follows:
- To determine whether pasireotide will inhibit cell proliferation and angiogenesis (signs of tumor growth), and stimulate apoptosis (cell death) in surgically excised tissue in comparison to core biopsies from women with estrogen receptor (ER) positive DCIS. Both the core biopsy and surgical excision are standard of care procedures that women with DCIS have regardless of participation in this trial.
- To use dynamic contrast enhanced MRI to assess patients before and after treatment with pasireotide and evaluate for changes in tumor volume and other tumor related features
- In our previous study we found that many women experienced a slight elevation in blood sugar with 10 days of treatment with pasireotide. Other work has shown that this effect often resolves with greater duration of treatment. We are therefore expanding the duration of treatment in this study to 20 days to assess if the initial hyperglycemia seen with pasireotide improves as treatment duration progresses.
Detailed description
Ductal carcinoma in situ (DCIS) is a direct precursor of invasive breast cancer and is also a marker of an increased chance of developing invasive cancer in the ipsilateral and contralateral breast. Surgery and radiotherapy are used as treatment for DCIS and subsequent treatment with antiestrogens has been effective in reducing the occurrence of invasive breast cancer in DCIS patients. Unfortunately, treatment with antiestrogens carries potential side effects and toxicities. The investigators have data to suggest that inhibition of IGF-I action in the breast will be more effective than antiestrogens, raising hopes it might be effective enough to stand alone as a treatment. Pasireotide is a somatostatin analog that prevents mammary development by inhibiting IGF-I action directly in the mammary gland and also indirectly, without causing menopausal symptoms and signs. As both estrogen (E2) and progesterone (P) require IGF-I in order to act, part of the inhibitory effect of pasireotide is on prevention of estrogen action. The investigators have data that indicate that IGF-I also has direct actions on the breast that are independent of steroid hormones. One example is that IGF-I has a direct stimulatory effect on mammary development in the absence of E2. Additionally, IGF-I has effects on ER-negative tumor cell lines that can be reversed by IGF-I inhibition. If pasireotide inhibited both E2 related and E2 unrelated effects of IGF-I it would likely be more effective than antiestrogens. Preliminary data in rats show that pasireotide, at minimum, can entirely substitute for tamoxifen. To determine whether pasireotide had activities in women at high risk for breast cancer, similar to those observed in rats, the investigators were awarded a DOD Synergistic Idea grant. Those data are expected to be reported soon.
The investigators plan to expand this work to determine in principle whether pasireotide has the potential to treat DCIS. The investigators plan on treating 24 women, with low grade (8), intermediate grade (8) and high grade (8) ER-positive DCIS tumors. The investigators will assess its effect on apoptosis, cell proliferation, angiogenesis, ER and PR and phosphorylation of IGF-IR and IRS-1 before and after 20 days of treatment with pasireotide in core biopsy vs. surgical excision specimens. These endpoints will be measured by specific immunohistochemistry. Simultaneously, the investigators will determine whether IGF-I inhibition will reduce angiogenesis in DCIS using dynamic contrast enhanced MRI (DCE-MRI) at 3.0 Tesla, in addition to mammography. This MRI technique is able to detect early changes of neo-angiogenesis associated with invasive breast cancers and DCIS. Pasireotide should theoretically inhibit angiogenesis in these women, as it does in mice. The DCE-MRI may also show changes in tumor volume, morphologic and kinetic features. Imaging will serve as an additional measure to monitor response to treatment. Results will be correlated with pathology and immunohistochemical endpoints.
In our previous work the investigators noted that there was an increase in blood glucose early after starting pasireotide, but the work of others has indicated that this side effect lasts only several weeks. The investigators found that suppressed levels of insulin (due to pasireotide effect on β cells) began to rise by day 10 of treatment. Therefore, extending the treatment period from 10 to 20 days with daily monitoring of patients will enable us to make certain that the early elevated glucose associated with pasireotide is only temporary. Another side effect is reduction in circulating levels of IGF-I. Theoretically, this could lead to body changes associated with growth hormone deficiency (GHD). Although, tamoxifen and raloxifene also lower serum IGF-I, and women taking it do not usually complain of symptoms of GHD, this is an issue that must be further investigated. However, if pasireotide is found to be effective in the treatment of DCIS, the benefit would likely outweigh the risk.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SOM 230/Pasireotide | Experimental | Drug: SOM 230 / PasireotideTreatment with SOM230 600mcg twice daily for 20 days. |
Who may qualify
- Ages
- 21 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 21 years of age and older
- Must sign informed consent, witnessed, and dated prior to entry
- The participant has breast biopsy consistent with Ductal Carcinoma in situ (DCIS)
- Performance Status: ECOG 0-1 unless mobility is limited from chronic physical handicap
- No clinical evidence of other malignancies (except Basal Cell carcinoma)
Key exclusion criteria (25 listed)
- Less than 21 years of age
- Known invasive breast cancer of any type
- Bilateral prophylactic mastectomy
- Prior malignancy of any type that occurred less than 5 years previously, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- Existing non-malignant disease that would preclude the administration of pasireotide
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 |
|---|---|---|
| SOM 230 / PasireotideSOM230/Pasireotide is a multi-receptor targeted somatostatin analogue. In this trial, 600 mcg of SOM230/Pasireotide are taken twice daily subcutaneously. | Drug | SOM 230/Pasireotide |
Primary outcome
Cell Proliferation and Apoptosis
Time frame: Before and after 20 days of treatment
Tissue from initial diagnostic breast biopsies will be compared to the remaining tissue excised after treatment with SOM230. Tissue will be stained to measure cell proliferation and apoptosis (cell death).
2 secondary outcomes
Effect of SOM 230 / Pasireotide on Tumor Volume and Tumor Kinetics
Time frame: Before and after 20 days of treatment
Hyperglycemia
Time frame: Before and after 20 days of treatment with 3 month post-treatment follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2017.
- 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.
David L Kleinberg, MD principal investigator
NYU School of Medicine
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 SOM 230 / Pasireotide in people with Ductal Carcinoma in Situ, run by NYU Langone Health 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 25 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: stopped early, as of the sponsor's last update on 27 Dec 2017. 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 27 Dec 2017). 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?
Cell Proliferation and Apoptosis (time frame: Before and after 20 days of treatment). 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 27 Dec 2017.