Pembrolizumab-based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas

NCT03136055 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 169524NCI-2017-01728
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

This is a pilot study of pembrolizumab-based therapy in previously treated extrapulmonary poorly differentiated neuroendocrine carcinoma

Conditions

High Grade Malignant Neuroendocrine Carcinoma (Diagnosis)

Keywords

NEC

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the percentage of participants in the analysis population who demonstrated complete response (CR) or partial response (PR) radiographically according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by investigator. The analysis will include all subjects treated (ITT) who received at least one dose of the study treatment. If the final study consists of both Part A and Part B, the analysis will be done separately for each part.

  Approximately 2 years

Secondary Outcomes (3)

• Overall Survival (OS)

  Over the duration of the study, which is estimated to be approximately 32 months.

• Duration of Response (DOR)

  Over the duration of the study, which is estimated to be approximately 32 months.

• Progression Free Survival (PFS)

  Over the duration of the study, which is estimated to be approximately 32 months.

Study Arms (2)

Part A: Pembrolizumab only

EXPERIMENTAL

Participants will receive 200 mg of pembrolizumab via IV over 30 minutes every 3 weeks for 24 months or 35 administrations (whichever comes first).

Drug: Pembrolizumab

Part B: Pembrolizumab + Chemotherapy

EXPERIMENTAL

Participants will receive 200 mg of pembrolizumab via IV over 30 minutes every 3 weeks for 24 months or 35 administrations (whichever comes first) and chemotherapy treatment of 125 mg/m\^2 of irinotecan via IV on days 1 and 8 of each 21-day cycle or paclitaxel via IV on days 1, 8, and 15 of each 21-day cycle per physician discretion

Drug: Pembrolizumab; Drug: Irinotecan; Drug: Paclitaxel

Interventions

Pembrolizumab DRUG

Given Intravenously (IV)

Also known as: Keytruda

Part A: Pembrolizumab only; Part B: Pembrolizumab + Chemotherapy

Irinotecan DRUG

Given IV

Also known as: Camptosar

Part B: Pembrolizumab + Chemotherapy

Paclitaxel DRUG

Given IV

Also known as: Taxol

Part B: Pembrolizumab + Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be at least 18 years of age on day of signing informed consent.
• Have a histologically proven locally advanced or metastatic high grade (G3) poorly differentiated neuroendocrine carcinoma (NEC).
• Includes small cell and large cell neuroendocrine carcinoma of unknown primary or any extrapulmonary site (and poorly differentiated NEC, not otherwise specified)
• Includes neuroendocrine prostate cancer (de novo or treatment-emergent) of prostate if small cell or large cell histology (histologic evidence of both adenocarcinoma and neuroendocrine carcinoma may be present in same patient).
• Other mixed tumors, e.g. mixed neuroendocrine neoplasms (MINENs) with NEC plus adenocarcinoma, squamous or acinar cell component are allowed if the high grade (small or large cell) NEC component comprises \>50% of the original sample or subsequent biopsy.
• Have progressed during or after completion of first line systemic chemotherapy.
• No limit to the number of prior chemotherapy regimens.
• Early progression on/after adjuvant chemotherapy counts as firstline therapy.
• Have at least one measurable disease based on RECIST 1.1.
• Patients must agree to have a biopsy of primary tumor or metastatic tissue at baseline, and there must be a lesion that can be biopsied with acceptable clinical risk (as judged by the investigator).
• Patients with unsuccessful baseline biopsies may undergo an additional biopsy attempt (at the same or a different site, determined by the investigator).
• For patients with an intact primary and no metastatic site that can be safely biopsied, biopsy of the primary is acceptable, but must be approved by the principal investigator.
• Baseline tumor biopsy may be omitted if the tumor is inaccessible and/or a biopsy is not thought to post exceptionally high procedural risk due to location or other factors
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

You may not qualify if:

• Has Merkel cell carcinoma, small cell lung carcinoma, or large cell NEC of lung
• Intermediate grade neuroendocrine tumors are excluded
• Well differentiated Grade 3 neuroendocrine tumors are excluded
• Metastatic high-grade prostate carcinoma with evidence of focal neuroendocrine differentiation on prostate biopsy (e.g., positive chromogranin staining by immunohistochemistry) without small cell or large cell NEC morphology are excluded, as are neuroendocrine prostate cancers with phenotype intermediate between adenocarcinoma and small cell
• Atypical and typical bronchial carcinoids and well differentiated G1 and G2 gastroenteropancreatic (GEP) neuroendocrine tumors (NET) (GEP NETs) are excluded.
• 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.
• Has a diagnosis of immunodeficiency
• Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• \- Physiologic doses of steroids (e.g. =\< 10 mg prednisone/day or equivalent) are allowed
• Has a known history of active Bacillus Tuberculosis (TB).
• History of or high suspicion of Gilbert's disease (safety run-in, Part B only)
• 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.
• Documented progression on and/or intolerance/hypersensitivity to both paclitaxel and irinotecan (Part B only)
• 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., \<= Grade 1 or at baseline) from adverse events due to a previously administered agent.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Raj N, Chan JA, Wang SJ, Aggarwal RR, Calabrese S, DeMore A, Fong L, Grabowsky J, Hope TA, Kolli KP, Mulvey CK, Munster PN, Perez K, Punn S, Reidy-Lagunes D, Von Fedak S, Zhang L, Bergsland EK. Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas. Br J Cancer. 2023 Aug;129(2):291-300. doi: 10.1038/s41416-023-02298-8. Epub 2023 May 19.

  PMID: 37208512 DERIVED

MeSH Terms

Conditions

Disease

Interventions

pembrolizumab; Irinotecan; Paclitaxel

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. Emily Bergsland
• Organization: University of California, San Francisco

Emily.Bergsland@ucsf.edu

(415) 353-9888

Study Officials

• Emily Bergsland, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: May 2, 2017
• Study Start: June 20, 2017
• Primary Completion: October 31, 2021
• Study Completion: October 31, 2021
• Last Updated: December 27, 2022
• Results First Posted: December 27, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)