Gastroenteropancreatic Neuroendocrine TumorsPhase 1/2PLANETNCT03043664
Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors
A Phase 1/2 study testing Lanreotide and Pembrolizumab in people with Gastroenteropancreatic Neuroendocrine Tumors, run by Duke University at 2 sites in United States.
Trial summary
This study is for patients with non-resectable, recurrent, or metastatic well or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The study will be conducted in two stages: 1) Safety Run-In and 2) Expanded Cohort. 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastroenteropancreatic Neuroendocrine Tumors
- What is being tested?
- Lanreotide and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jul 2017to 7 Jun 2022
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent for the trial.
- At least 18 years of age on day of signing informed consent.
- Non-resectable, recurrent, or metastatic well- or moderately-differentiated gastroenteropancreatic neuroendocrine tumor (GEP-NETs) with disease progression within the last 12 months. (Patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of > 20% in the size. Prior local therapy must be completed at least 4 weeks prior to the baseline scan.)
- Prior somatostatin analogue therapy. (Patients should receive the first dose of study drug no sooner than 4 weeks from the last dose of somatostatin analogue.)
- At least one measurable lesion based on RECIST version 1.1.
- Agrees to provide available archived tumor tissue specimen. (Patients who do not have available archived tumor must agree to have core or excisional biopsy of a tumor lesion obtained up to 42 days prior to the first dose of study drug, if safely accessible. If archived tissue is not available and the tumor is not amenable to safe biopsy, subject is still eligible to participate.)
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- ECOG performance status of 0 or 1.
- Adequate organ function defined as:
- Absolute neutrophil count (ANC) ≥ 1,500 /mcL
- Platelets ≥ 100,000 /mcL
- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
- Serum creatinine OR calculated creatinine clearance (CrCL) per institutional standard (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
- Serum total bilirubin ≤ 1.5 X ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
- Albumin ≥ 2.5 mg/dL
- Negative serum pregnancy test within ≤ 7 days prior to the first dose of study drug, for women of childbearing potential only.
- Female subjects agree to use two birth control methods, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study drug.
- Male subjects agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
Who cannot join
- Tumor mitotic rate >20/10 hpf and/or Ki67 index >20% (if available).
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Known history of active TB (Bacillus Tuberculosis).
- Hypersensitivity to pembrolizumab or lanreotide or any of their excipients.
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
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- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Prior major surgery within 2 weeks prior to the first dose of study drug or who has not recovered adequately from the toxicity and/or complications from the intervention.
- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to the first dose of study drug. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Known history of, or any evidence of active, non-infectious pneumonitis.
- Active infection requiring systemic therapy.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating physician.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of study drug.
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Live vaccine within 30 days of planned start of study drug regimen. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- History of intolerance to somatostatin analogues.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Lexington Medical Center
Columbia, South Carolina, 29169
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Phase Ib/II Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors
This study is for patients with non-resectable, recurrent, or metastatic well or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
The study will be conducted in two stages: 1) Safety Run-In and 2) Expanded Cohort.
- Safety run-in: The first stage will include a safety run-in of 6 patients treated with pembrolizumab 200 mg intravenous (IV) every 3 weeks and lanreotide depot 90mg subcutaneous (SQ) every 3 weeks. Up to 6 patients at the Duke Cancer Institute will be accrued at the starting dose level. If one or less subject meets treatment-related discontinuation criteria (as specified in the protocol) during Cycle 1, then the study will proceed to the second stage, Expanded Cohort.
- Expanded Cohort: Patients will be treated with pembrolizumab 200mg IV every 3 weeks and lanreotide depot 90mg SQ every 3 weeks as determined by the Safety Run-In Cohort.
- Being tested
- Lanreotide, Pembrolizumab
- Keywords
- GEP-NET, pembrolizumab, lanreotide, PD-1, Keytruda, Somatuline Depot, PD-L1, anti-PD-1
- Medical subject headings
- Gastro-enteropancreatic neuroendocrine tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LanreotideDrug
Also called Somatuline Depot
Somatuline depot (lanreotide) 90 mg SQ every 3 weeks
PembrolizumabDrug
Also called Keytruda
Keytruda (pembrolizumab) 200 mg IV every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks. Receives: Drug: Lanreotide; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion. A 90% LCB of < 0.1 will be considered not to be of clinical value. If the 90% LCB is ≥ 0.1, the regimen will be considered efficacious.
Measured: Approximately every 12 weeks until study completion (up to 2 years)
Secondary outcomes (4)
Number of Participants Experiencing Treatment-related AEs Leading to Drug Discontinuations During the First 12 Weeks of Treatment
Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measured: First 12 weeks of treatment
Months of Progression-free Survival (PFS)
Months from treatment start date until the date of first documented radiographic progression or date of death from any cause (whichever is first); assessed up to 48 weeks after the last subject has finished study drug regimen. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Measured: Up to 3 years
Months of Overall Survival (OS)
Months from treatment start date until the date of death from any cause; assessed up to 48 weeks after the last subject has finished the study drug regimen
Measured: Up to 59 months
ORR as Measured by Immune-related Response Criteria (irRC)
Treatment response as assessed by irRC instead of RECIST v1.1. ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as complete disappearance of all lesions (whether measurable or not, and no new lesions), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date first documented. Partial response is defined as a decrease in tumor burden ≥ 50% relative to baseline, confirmed by a consecutive assessment at least 4 weeks after first documentation. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion.
Measured: Approximately every 12 weeks until study completion (up to 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2017 (estimated)
- Study start1 Jul 2017
- Primary completion3 May 2021
- Study completion7 Jun 2022
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 Gastroenteropancreatic Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Model description
- Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Ipsen
- Responsible party
- Sponsor
- Investigators
- Michael Morse, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03043664
- Sponsor's protocol ID
- Pro00074917
- Acronym
- PLANET
- Status last verified
- Jun 2023
- First submitted
- 1 Feb 2017
- Last updated
- 29 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT03043664
- Acronym / sponsor ID
- PLANET / Pro00074917
- Keywords
- GEP-NET, pembrolizumab, lanreotide, PD-1, Keytruda, Somatuline Depot, PD-L1, anti-PD-1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Ipsen
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 3 May 2021 (actual)
- Study completion
- 7 Jun 2022 (actual)
- First posted
- 6 Feb 2017 (estimated)
- Results
- Posted 28 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is for patients with non-resectable, recurrent, or metastatic well or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
The study will be conducted in two stages: 1) Safety Run-In and 2) Expanded Cohort.
- Safety run-in: The first stage will include a safety run-in of 6 patients treated with pembrolizumab 200 mg intravenous (IV) every 3 weeks and lanreotide depot 90mg subcutaneous (SQ) every 3 weeks. Up to 6 patients at the Duke Cancer Institute will be accrued at the starting dose level. If one or less subject meets treatment-related discontinuation criteria (as specified in the protocol) during Cycle 1, then the study will proceed to the second stage, Expanded Cohort.
- Expanded Cohort: Patients will be treated with pembrolizumab 200mg IV every 3 weeks and lanreotide depot 90mg SQ every 3 weeks as determined by the Safety Run-In Cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Lanreotide, Drug: PembrolizumabKeytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Willing and able to provide written informed consent for the trial.
- At least 18 years of age on day of signing informed consent.
- Non-resectable, recurrent, or metastatic well- or moderately-differentiated gastroenteropancreatic neuroendocrine tumor (GEP-NETs) with disease progression within the last 12 months. (Patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of > 20% in the size. Prior local therapy must be completed at least 4 weeks prior to the baseline scan.)
- Prior somatostatin analogue therapy. (Patients should receive the first dose of study drug no sooner than 4 weeks from the last dose of somatostatin analogue.)
- At least one measurable lesion based on RECIST version 1.1.
Key exclusion criteria (21 listed)
- Tumor mitotic rate >20/10 hpf and/or Ki67 index >20% (if available).
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Known history of active TB (Bacillus Tuberculosis).
- Hypersensitivity to pembrolizumab or lanreotide or any of their excipients.
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 |
|---|---|---|
| LanreotideAlso: Somatuline DepotSomatuline depot (lanreotide) 90 mg SQ every 3 weeks | Drug | Arm 1 |
| PembrolizumabAlso: KeytrudaKeytruda (pembrolizumab) 200 mg IV every 3 weeks | Drug | Arm 1 |
Primary outcome
Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: Approximately every 12 weeks until study completion (up to 2 years)
ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion. A 90% LCB of < 0.1 will be considered not to be of clinical value. If the 90% LCB is ≥ 0.1, the regimen will be considered efficacious.
4 secondary outcomes
Number of Participants Experiencing Treatment-related AEs Leading to Drug Discontinuations During the First 12 Weeks of Treatment
Time frame: First 12 weeks of treatment
Months of Progression-free Survival (PFS)
Time frame: Up to 3 years
Months of Overall Survival (OS)
Time frame: Up to 59 months
ORR as Measured by Immune-related Response Criteria (irRC)
Time frame: Approximately every 12 weeks until study completion (up to 2 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Michael Morse, MD principal investigator
Duke University
2 sites 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 Lanreotide and Pembrolizumab in people with Gastroenteropancreatic Neuroendocrine Tumors, run by Duke University at 2 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 18 inclusion and 21 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 29 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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 28 Sep 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?
Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (time frame: Approximately every 12 weeks until study completion (up to 2 years)). 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 29 Jun 2023; AzTrials last refreshed its copy on 8 Nov 2026.