A Study of Pembrolizumab in Patients With Neuroendocrine Tumors

• ClinicalTrials.gov Identifier: NCT02939651
• Recruitment Status: Completed
• First Posted: October 20, 2016
• Results First Posted: March 9, 2021
• Last Update Posted: March 9, 2021
• Sponsor: Fox Chase Cancer Center
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Fox Chase Cancer Center

Study Description

Brief Summary:

The purpose of this research study is to test if pembrolizumab is safe and effective for treating patients with metastatic high-grade neuroendocrine tumors who have failed platinum based chemotherapy.The study drug, pembrolizumab has been FDA approved for treating a type of skin cancer called melanoma and for metastatic non-small cell lung cancer. However, it is not approved for treatment of metastatic high-grade neuroendocrine tumors.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumors	Drug: Pembrolizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label Study of Pembrolizumab Monotherapy in Patients With Metastatic High Grade Neuroendocrine Tumors
• Actual Study Start Date: October 26, 2016
• Actual Primary Completion Date: February 2018
• Actual Study Completion Date: March 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pembrolizumab; Monotherapy with PD-1 antibody pembrolizumab	Drug: Pembrolizumab; Pembrolizumab given intravenously at a fixed dose of 200mg every 3 weeks; Other Names: Keytruda; MK-3475

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Upto 3 years ]
   To estimate objective response rate (ORR), using RECIST 1.1, in previously treated metastatic High Grade Neuroendocrine Tumors (HGNET) patients treated with pembrolizumab monotherapy. The Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria will be used for objective tumor response assessment: Complete Response (CR):Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

Secondary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: Upto 3 years ]
   To evaluate progression free survival (PFS) (using RECIST 1.1) in metastatic HGNET patients treated with pembrolizumab monotherapy. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase (at least 5 mm absolute increase) in the sum of the longest diameter of target lesions. PFS was estimated according to the Kaplan-Meier method.
2. Overall Survival [ Time Frame: Upto 3 years ]
   To evaluate overall survival (OS) in metastatic HGNET patients treated with pembrolizumab monotherapy. OS was estimated according to the Kaplan-Meier method.
3. Frequency With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: Upto 3 years ]
   Occurence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed metastatic, high grade NET (Ki67 >20%), excluding any high grade NETs of large or small cell type of lung/thymus origin and merkel cell carcinoma
2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 12.0
3. Has received prior therapy with at least 1 platinum-containing regimen
4. Age > 18 years.
5. ECOG performance status 0 or 1
6. Patients must have normal organ and marrow function
7. Female participants of childbearing potential must have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication). They should also be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
8. Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
9. Ability to understand and willingness to sign a written informed consent and HIPAA consent document

Exclusion Criteria:

1. 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 trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
2. Is 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 treatment.
3. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
4. Prior anti-cancer therapy with a monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from adverse events (improved to grade 1 or less) due to mAbs administered more than 4 weeks earlier.
5. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks (12 weeks for measurable sites of CNS disease) prior to study Day 1 or not recovered from adverse events (improved to grade 1 or less) due to a previously administered agent. Note: Subjects with neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
6. Known additional malignancy that is progressing or requires active treatment except superficial malignancies of the skin and in situ cervical cancer
7. Has an 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.
8. Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active non-infectious pneumonitis.
9. Active infection requiring systemic therapy at enrollment.
10. Has a known history of active TB (Bacillus Tuberculosis)
11. Hypersensitivity to pembrolizumab or any of its excipients
12. Has received a live virus vaccine within 30 days of planned start of trial treatment.
13. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening period through 120 days after the last dose of trial treatment
14. Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
15. Known history of human immunodeficiency virus (HIV)
16. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative]).
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
18. Has a 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 investigator.

Contacts and Locations

Locations

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States

Sponsors and Collaborators

Fox Chase Cancer Center

Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Namrata Vijayvergia, MD; Fox Chase Cancer Center

  Study Documents (Full-Text)

Documents provided by Fox Chase Cancer Center:

Study Protocol and Statistical Analysis Plan  [PDF] March 3, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vijayvergia N, Dasari A, Deng M, Litwin S, Al-Toubah T, Alpaugh RK, Dotan E, Hall MJ, Ross NM, Runyen MM, Denlinger CS, Halperin DM, Cohen SJ, Engstrom PF, Strosberg JR. Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials. Br J Cancer. 2020 Apr;122(9):1309-1314. doi: 10.1038/s41416-020-0775-0. Epub 2020 Mar 10.

• Responsible Party: Fox Chase Cancer Center
• ClinicalTrials.gov Identifier: NCT02939651
• Other Study ID Numbers: GI-087
• First Posted: October 20, 2016
• Results First Posted: March 9, 2021
• Last Update Posted: March 9, 2021
• Last Verified: February 2021

Keywords provided by Fox Chase Cancer Center:

Metastatic; High grade

Additional relevant MeSH terms:

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents