Neuroendocrine CarcinomaPhase 2NCT01121939
Combination of Bevacizumab, Pertuzumab, and Sandostatin for Adv. Neuroendocrine Cancers
A Phase 2 study testing Bevacizumab, Pertuzumab and Sandostatin LAR® Depot in people with Neuroendocrine Carcinoma, run by SCRI Development Innovations, LLC at 9 sites in United States.
Trial summary
The purpose of this Phase II trial will be to define the activity of a VEGF inhibitor bevacizumab, HER1/HER2 inhibitor pertuzumab, and sandostatin for patients with advanced neuroendocrine cancers. In particular, the efficacy of bevacizumab and pertuzumab treatment is of great interest. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Carcinoma
- What is being tested?
- Bevacizumab, Pertuzumab and Sandostatin LAR® Depot
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 9 sitesUnited States
- Study dates
- May 2010to Aug 2015
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with biopsy-proven advanced, unresectable or metastatic, well-differentiated (or low-grade) neuroendocrine carcinoma, including typical carcinoid, pancreatic islet cell and other well-differentiated neuroendocrine carcinomas.
- Patients with documented evidence of disease progression.
- Patients currently receiving or previously treated with single agent Sandostatin LAR® are eligible.
- Patients must have >=1 unidimensional measurable lesion definable by
- MRI or CT scan. Disease must be measurable per RECIST version 1.1 criteria.
- Left Ventricular Ejection Fraction (LVEF) >=50% as determined by either ECHO or MUGA <=6 weeks prior to study entry.
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- An ECOG Performance Status of 0-2.
- Laboratory values as follows:
- ANC >=1500/μL
- Hgb >=9 g/dL
- Platelets >=100,000/μL
- AST/SGOT <=2.5 x ULN or <=5.0 x ULN in patients with liver metastases
- ALT/SGPT <=2.5 x ULN or <=5.0 x ULN in patients with liver metastases
- Bilirubin <=1.5 x ULN
- Creatinine <=2.0 mg/dL or calculated creatinine clearance >=50 mL/min
- Patients >=18 years of age.
- Patients must have a life expectancy >12 weeks.
- Patient must be accessible for treatment and follow-up.
- Women of childbearing potential must have a negative serum or urine pregnancy test performed <=7 days prior to start of treatment. Women of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
- Patients must be able to understand the nature of the study and give
- written informed consent, and comply with study requirements
Who cannot join
- Patients with poorly differentiated neuroendocrine carcinoma, highgrade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid, atypical carcinoid, anaplastic carcinoid, and small cell carcinoma are not eligible.
- Previous treatment with VEGF or EGFR inhibitors.
- Cytotoxic chemotherapy, immunotherapy or radiotherapy <=4 weeks prior to study entry.
- History or known presence of central nervous system (CNS) metastases.
- Patients who have had a major surgical procedure (not including mediastinoscopy), open biopsy, or significant traumatic injury <=4 weeks prior to beginning treatment.
- Female patients who are pregnant or lactating.
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- History of hypersensitivity to active or inactive excipients of any component of treatment (bevacizumab, sandostatin, and/or pertuzumab).
- Patients with proteinuria at screening as demonstrated by urine dipstick for proteinuria >=2+ (patients discovered to have >=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection, and must demonstrate <=1 g of protein/24 hours to be eligible).
- Patients with a serious non-healing wound, active ulcer, or untreated bone fracture.
- Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
- Patients with history of hematemesis or hemoptysis (defined as having bright red blood of ½ teaspoon or more per episode) <=1 month prior to study enrollment.
- History of myocardial infarction or unstable angina <=6 months prior to beginning treatment.
- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and /or diastolic blood pressure >100 mmHg while on antihypertensive medications). Initiation of antihypertensive agents is permitted provided adequate control is documented at least 1 week prior to Day of study treatment.
- New York Heart Association (NYHA) grade II or greater congestive
- heart failure (CHF).
- Serious cardiac arrhythmia requiring medication.
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) <=6 months prior to Day 1 of treatment.
- History of stroke or transient ischemic attack <=6 months prior to beginning treatment.
- Any prior history of hypertensive crisis or hypertensive encephalopathy.
- History of abdominal fistula or gastrointestinal perforation <=6 months prior to Day 1 of beginning treatment.
- Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Any known positive test for human immunodeficiency virus, hepatitis C virus or acute or chronic hepatitis B infection.
- Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
- Use of any non-approved or investigational agent <=28 days prior to administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
- Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a DFS >=5 years.
- Infection requiring IV antibiotics.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Medical Oncology Associates of Augusta
Augusta, Georgia, 30901
Oncology Hematology Care, Inc
Cincinnati, Ohio, 45242
Florida Cancer Specialists
Fort Myers, Florida, 33901
Grand Rapids Oncology Program
Grand Rapids, Michigan, 49503
Research Medical Center
Kansas City, Missouri, 64132
Baptist Medical Center East
Louisville, Kentucky, 40207
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, 07960
Tennessee Oncology Associates
Nashville, Tennessee, 37203
Florida Hospital Cancer Institute
Orlando, Florida, 32804
About this study
Official title: Phase II Study of the Combination of Bevacizumab, Pertuzumab, and Sandostatin for Patients With Advanced Neuroendocrine Cancers.
The purpose of this Phase II trial will be to define the activity of a VEGF inhibitor
bevacizumab, HER1/HER2 inhibitor pertuzumab, and sandostatin for patients with
advanced neuroendocrine cancers. In particular, the efficacy of bevacizumab and
pertuzumab treatment is of great interest. The primary endpoint of this trial will be
response rate. Toxicity and progression-free survival will be obtained and evaluated.
Read the detailed description
- To determine overall response rate of patients with low grade neuroendocrine cancer when treated with the combination of bevacizumab, pertuzumab and sandostatin LAR®.
- To determine the disease control rate (objective response + stable disease), time to treatment progression, progression-free survival, and overall survival in patients with advanced low grade neuroendocrine cancer when treated with bevacizumab, pertuzumab and Sandostatin LAR® treatment.
- To define the toxicity and safety of the combination of bevacizumab, pertuzumab and Sandostatin LAR® when used in patients with advanced low grade neuroendocrine cancer.
- Conditions
- Neuroendocrine Carcinoma
- Being tested
- Bevacizumab, Pertuzumab, Sandostatin LAR® Depot
- Keywords
- advanced neuroendocrine, Gastrointestinal, Bevacizumab, Avastin, Pertuzumab, Omnitarg, 2C4, Sandostatin, Octreotide
- Medical subject headings
- Carcinoma, Neuroendocrine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
15 mg/kg IV Day 1. The first dose should be administered over
90 minutes. If no adverse reactions occur after the initial dose, the second dose should
be administered over a minimum of 60 minutes. If no adverse reactions occur after the
second dose, all subsequent doses should be administered over a minimum of 30
minutes. Bevacizumab will be infused prior to pertuzumab.
PertuzumabDrug
Also called Omnitarg, 2C4
840 mg IV loading dose infused over 60 minutes. The loading dose is given on Cycle 1, Day 1 or as below. Subsequent doses of pertuzumab are 420 mg IV. If the patient tolerates the initial infusion over 60 minutes, the patient may receive subsequent infusions over 30 minutes. Otherwise, pertuzumab should be infused over 60 minutes. Patients should be observed for 30 minutes after completing the pertuzumab infusion.
If a patient misses a dose of pertuzumab for 1 cycle (i.e., 2 sequential cycles or administrations are 6 weeks or more apart), a re-loading dose (840 mg) of pertuzumab should be given. If re-loading pertuzumab is administered, subsequent doses of 420 mg will then be given every 3 weeks, starting 3 weeks later.
Sandostatin LAR® DepotDrug
Also called Octreotide
30 mg will be given every 28 days by IM injection. The dose of sandostatin may be increased, at the discretion of the treating physician, if necessary to control symptoms related to tumor secretion of vasoactive peptides.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | combination of bevacizumab, pertuzumab, and sandostatin for patients with advanced neuroendocrine cancers Receives: Drug: Bevacizumab; Drug: Pertuzumab; Drug: Sandostatin LAR® Depot |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 18 months
Secondary outcomes (4)
Define Toxicity and Safety
To define the toxicity and safety of the combination of bevacizumab, pertuzumab and Sandostatin LAR® when used in patients with advanced low grade neuroendocrine cancer - defined by grade 3/4, treatment-related toxicity
Measured: 18 months
Progression-Free Survival (PFS)
The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 18 months
Overall Survival (OS)
The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Measured: 18 months
Disease Control Rate
The Percentage of Patients Who Experience an Objective Benefit From Treatment or Experience Stable Disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither Sufficient Shrinkage to Qualify For PR, Nor Sufficient Increase to Qualify for Progressive Disease; Disease Control Rate = CR + PR + SD.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2010 (estimated)
- Study startMay 2010
- Primary completionFeb 2015
- Study completionAug 2015
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 Neuroendocrine CarcinomaStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Johanna C Bendell, S.B., M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01121939
- Sponsor's protocol ID
- SCRI GI 135
- Status last verified
- Jan 2016
- First submitted
- 10 May 2010
- Last updated
- 5 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of the Combination of Bevacizumab, Pertuzumab, and Sandostatin for Patients With Advanced Neuroendocrine Cancers.
- ClinicalTrials.gov ID
- NCT01121939
- Acronym / sponsor ID
- SCRI GI 135
- Conditions
- Neuroendocrine Carcinoma
- Keywords
- advanced neuroendocrine, Gastrointestinal, Bevacizumab, Avastin, Pertuzumab, Omnitarg, 2C4, Sandostatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- May 2010
- Primary completion
- Feb 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 12 May 2010 (estimated)
- Results
- Posted 23 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase II trial will be to define the activity of a VEGF inhibitor
bevacizumab, HER1/HER2 inhibitor pertuzumab, and sandostatin for patients with
advanced neuroendocrine cancers. In particular, the efficacy of bevacizumab and
pertuzumab treatment is of great interest. The primary endpoint of this trial will be
response rate. Toxicity and progression-free survival will be obtained and evaluated.
Detailed description
- To determine overall response rate of patients with low grade neuroendocrine cancer when treated with the combination of bevacizumab, pertuzumab and sandostatin LAR®.
- To determine the disease control rate (objective response + stable disease), time to treatment progression, progression-free survival, and overall survival in patients with advanced low grade neuroendocrine cancer when treated with bevacizumab, pertuzumab and Sandostatin LAR® treatment.
- To define the toxicity and safety of the combination of bevacizumab, pertuzumab and Sandostatin LAR® when used in patients with advanced low grade neuroendocrine cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Bevacizumab, Drug: Pertuzumab, Drug: Sandostatin LAR® Depotcombination of bevacizumab, pertuzumab, and sandostatin for patients with advanced neuroendocrine cancers |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients with biopsy-proven advanced, unresectable or metastatic, well-differentiated (or low-grade) neuroendocrine carcinoma, including typical carcinoid, pancreatic islet cell and other well-differentiated neuroendocrine carcinomas.
- Patients with documented evidence of disease progression.
- Patients currently receiving or previously treated with single agent Sandostatin LAR® are eligible.
- Patients must have >=1 unidimensional measurable lesion definable by
- MRI or CT scan. Disease must be measurable per RECIST version 1.1 criteria.
Key exclusion criteria (26 listed)
- Patients with poorly differentiated neuroendocrine carcinoma, highgrade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid, atypical carcinoid, anaplastic carcinoid, and small cell carcinoma are not eligible.
- Previous treatment with VEGF or EGFR inhibitors.
- Cytotoxic chemotherapy, immunotherapy or radiotherapy <=4 weeks prior to study entry.
- History or known presence of central nervous system (CNS) metastases.
- Patients who have had a major surgical procedure (not including mediastinoscopy), open biopsy, or significant traumatic injury <=4 weeks prior to beginning treatment.
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 |
|---|---|---|
| BevacizumabAlso: Avastin15 mg/kg IV Day 1. The first dose should be administered over 90 minutes. If no adverse reactions occur after the initial dose, the second dose should be administered over a minimum of 60 minutes. If no adverse reactions occur after the second dose, all subsequent doses should be administered over a minimum of 30 minutes. Bevacizumab will be infused prior to pertuzumab. | Drug | 1 |
| PertuzumabAlso: Omnitarg, 2C4840 mg IV loading dose infused over 60 minutes. The loading dose is given on Cycle 1, Day 1 or as below. Subsequent doses of pertuzumab are 420 mg IV. If the patient tolerates the initial infusion over 60 minutes, the patient may receive subsequent infusions over 30 minutes. Otherwise, pertuzumab should be infused over 60 minutes. Patients should be observed for 30 minutes after completing the pertuzumab infusion. If a patient misses a dose of pertuzumab for 1 cycle (i.e., 2 sequential cycles or administrations are 6 weeks or more apart), a re-loading dose (840 mg) of pertuzumab should be given. If re-loading pertuzumab is administered, subsequent doses of 420 mg will then be given every 3 weeks, starting 3 weeks later. | Drug | 1 |
| Sandostatin LAR® DepotAlso: Octreotide30 mg will be given every 28 days by IM injection. The dose of sandostatin may be increased, at the discretion of the treating physician, if necessary to control symptoms related to tumor secretion of vasoactive peptides. | Drug | 1 |
Primary outcome
Objective Response Rate (ORR)
Time frame: 18 months
The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
4 secondary outcomes
Define Toxicity and Safety
Time frame: 18 months
Progression-Free Survival (PFS)
Time frame: 18 months
Overall Survival (OS)
Time frame: 18 months
Disease Control Rate
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Neuroendocrine Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
RecruitingPhase 3
Somatostatin Analogues vs. Observation After Peptide Receptor Radionuclide Therapy (PRRT) in Nonfunctional Neuroendocrine Neoplasms
Neuroendocrine Neoplasm, Gastroenteropancreatic Neuroendocrine Neoplasm
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
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.
Johanna C Bendell, S.B., M.D. study chair
SCRI Development Innovations, LLC
9 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 Bevacizumab, Pertuzumab and Sandostatin LAR® Depot in people with Neuroendocrine Carcinoma, run by SCRI Development Innovations, LLC at 9 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?
The sponsor lists 21 inclusion and 26 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 5 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 23 Sep 2015). 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?
Objective Response Rate (ORR) (time frame: 18 months). 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 5 Feb 2016.