Pembrolizumab for the Treatment of Recurrent High Grade Neuroendocrine Carcinoma

NCT03190213 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCI102310
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, non-randomized phase 2 study to assess overall response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and progression free survival (PFS) in patients with high grade neuroendocrine tumors treated with pembrolizumab 200mg Q 3 Weeks.

Conditions

Neuroendocrine Tumors

Keywords

high grade

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response was measured using Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST). At baseline, lesions found on CT or MRI imaging are cataloged as "target" or "non-target" lesions, and the longest dimensions of target lesions (or shortest dimension of target lymph nodes) are summed. irRECIST defines Complete Response (irCR) as a complete disappearance of all lesions after baseline. Partial Response (irPR) is defined as a 30% or more decrease in the target lesion measurements. Overall response rate is defined the percentage of participants with a best response of irCR + irPR.

  planned for up to two years from baseline; actual time was up to 230 days (average of 70.5 days)

Secondary Outcomes (4)

• Clinical Benefit Rate

  planned for up to two years from baseline; actual time was up to 230 days (average of 70.5 days)

• Median Progression Free Survival

  planned for up to four years from baseline; actual time was up to 230 days (average of 70.5 days)

• Median Overall Survival

  planned for up to four years from baseline; actual time was up to 230 days (average of 70.5 days)

• Number of Patients With Adverse Events Reported

  planned for up to two years of treatment plus 90 days; actual time was up to 338 days (average of 170 days)

Study Arms (1)

Pembrolizumab, all patients

EXPERIMENTAL

Drug: Pembrolizumab Injection

Interventions

Pembrolizumab Injection DRUG

Pembrolizumab at a dose of 200 mg will be administered as an IV infusion over 30 minutes every 3 weeks until disease recurrence or discontinuation due to unacceptable toxicity for a maximum of 2 years. We anticipate on average patients will remain on treatment for approximately 24 weeks.

Pembrolizumab, all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, metastatic or unresectable neuroendocrine carcinoma of non-pulmonary origin, high grade as indicated by Ki-67 \>20% and/or \> 20 mitoses/10 hpf. Patients must have existing Ki-67 results from archival tissue or available tissue for Ki-67 testing. If no archival tissue is available the subject must agree to a fresh biopsy for testing to qualify for the study.
• Have measurable disease based on Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST).
• Be greater than or equal to 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function as defined in the protocol, all screening labs should be performed within 14 days of treatment initiation.
• Subjects with a history of known central nervous system (CNS) metastases must have documentation of stable or improved brain imaging for at least 2 weeks after completion of definitive treatment. Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should 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 Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male subjects should 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.
• Must have recovered from adverse effects of any prior surgery, radiotherapy or other antineoplastic therapy.
• Last dose of any antineoplastic therapy greater than or equal to 2 weeks (including chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents). Patients receiving hormone manipulation (e.g. selective estrogen receptor modulators (SERMs), aromatase inhibitors, luteinizing hormone-releasing hormone (LHRH} agonist, etc.) for reasons other than treatment of metastatic breast cancer may continue this treatment at the discretion of the investigator.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

You may not qualify if:

• 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 2 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or receiving steroid therapy of any other form of immunosuppressive therapy within 7 days prior to first dose of trial treatment. Subjects who receive daily steroid replacement therapy serve as an exception to this rule. Daily prednisone at doses of 5 to 7.5 mg (or hydrocortisone equivalent doses) is an example of replacement therapy.
• Has a known history of active Bacillus Tuberculosis (TB).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with less than or equal to Grade 2 neuropathy 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. Patients receiving hormone manipulation (e.g. tamoxifen, aromatase inhibitors, LHRH agonist, etc.) for reasons other than treatment of metastatic breast cancer may continue this treatment at the discretion of the investigator.
• Has a 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. Patients on long-term adjuvant therapy with no evidence of disease are not excluded if felt appropriate by investigator.
• Has 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 2 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.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, 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.
• Has known history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• 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.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is 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 trial treatment.
• Has received prior therapy with an anti-programmed death (PD) -1, anti-PD-L1, or anti-PD-L2 agent.

Sponsors & Collaborators

• University of Utah: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Data Manager
• Organization: Huntsman Cancer Institute Research Compliance Office

compliance@hci.utah.edu

8015850601

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open label, non-randomized phase 2 study

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 16, 2017
• Study Start: December 4, 2017
• Primary Completion: December 13, 2018
• Study Completion: March 11, 2019
• Last Updated: June 22, 2021
• Results First Posted: January 27, 2020

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)