Clinical Trials /

Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors

NCT03043664

Description:

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. 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. 2. 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.

Related Conditions:
  • Digestive System Neuroendocrine Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors
  • Official Title: Phase Ib/II Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors

Clinical Trial IDs

  • ORG STUDY ID: Pro00074917
  • NCT ID: NCT03043664

Conditions

  • Gastroenteropancreatic Neuroendocrine Tumors

Interventions

DrugSynonymsArms
Somatuline DepotArm 1
KeytrudaArm 1

Purpose

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. 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. 2. 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.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalKeytruda (pembrolizumab) 200 mg intravenous (IV) every 3 weeks and Somatuline Depot (lanreotide depot) 90mg subcutaneous (SQ) every 3 weeks
  • Somatuline Depot
  • Keytruda

Eligibility Criteria

        Inclusion Criteria:

          1. Willing and able to provide written informed consent for the trial.

          2. At least 18 years of age on day of signing informed consent.

          3. 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.)

          4. 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.)

          5. At least one measurable lesion based on RECIST version 1.1.

          6. 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.)

          7. ECOG performance status of 0 or 1 (refer to Appendix C).

          8. 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

          9. Negative serum pregnancy test within ≤ 7 days prior to the first dose of study drug,
             for women of childbearing potential only.

         10. 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.

         11. 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.

        Exclusion Criteria:

          1. Tumor mitotic rate >20/10 hpf and/or Ki67 index >20% (if available).

          2. 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.

          3. 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.

          4. Known history of active TB (Bacillus Tuberculosis).

          5. Hypersensitivity to pembrolizumab or lanreotide or any of their excipients.

          6. 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.

          7. 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.

          8. 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.

          9. 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.

         10. 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.

         11. 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.

         12. Known history of, or any evidence of active, non-infectious pneumonitis.

         13. Active infection requiring systemic therapy.

         14. 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.

         15. Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial.

         16. 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.

         17. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

         18. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         19. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         20. 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.

         21. History of intolerance to somatostatin analogues.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame:Approximately every 12 weeks and/or re-staging through study completion (up to 2 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Treatment-related adverse events
Time Frame:Continuous, at minimum every 3 weeks until study completion (up to 2 years)
Safety Issue:
Description:
Measure:Progression free survival (PFS) of pembrolizumab in combination with lanreotide depot in subjects with GEP-NETs.
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause (whichever is first); assessed up to 48 weeks after the last subject enrolled
Safety Issue:
Description:
Measure:Overall survival (OS) of pembrolizumab in combination with lanreotide depot in subjects with GEP-NETs.
Time Frame:From date of randomization until the date of death from any cause; assessed up to 48 weeks after the last subject enrolled
Safety Issue:
Description:
Measure:ORR by Immune-Related Response Criteria (irRC) to pembrolizumab in combination with lanreotide depot in subjects with progressive, advanced or metastatic GEP-NETs.
Time Frame:Approximately every 12 weeks and/or restaging until study completion (up to 2 years)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Duke University

Trial Keywords

  • GEP-NET
  • Pembrolizumab
  • Lanreotide depot
  • PD-1

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