Palliative RT & Anti-PD-1/PD-L1 Checkpoint Blockade in Metastatic Merkel Cell Carcinoma

NCT03988647 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB-50888SKIN0047
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to assess 1) the safety and 2) efficacy of combining Anti-PD-1/PD-L1 blockade with palliative radiation therapy in patients with Stage IV Merkel Cell Carcinoma.

Conditions

Merkel Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Tumor Response

  Tumor Response at both irradiated \& unirradiated sites will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Basic RECIST response will be assessed by the criterion below. * Complete Response (CR) = Disappearance of all target lesions. * Partial Response (PR) = ≥0% decrease in the sum of the longest diameter (LD) of target lesions. * Stable disease (SD) = Small changes that do not meet any of the above criteria. RECIST v1.1 immune-related response will be assessed by the criterion below. * Immune-related CR (irCR) = Disappearance of all target lesions. Lymph nodes \<10 mm in short axis. * Immune-related PR (irPR) = ≥30% decrease in the sum of the LD of target lesions. * Immune-related SD (irSD) = Failure to meet criteria for irCR or irPR in the absence of irPR. The outcome is reported as the number of lesions with each of the different levels of clinical response, a number without dispersion.

  15 months

Secondary Outcomes (2)

• Overall Survival (OS)

  18 months

• Duration of Response (DOR)

  15 months

Study Arms (1)

Pembrolizumab + Palliative Radiation Therapy

EXPERIMENTAL

Pembrolizumab will be administered at 200 mg IV every 3 weeks as standard of care. Palliative radiation therapy will be given between the first and second cycles of immunotherapy

Drug: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Pembrolizumab DRUG

Pembrolizumab administered at 200 mg IV every 3 weeks

Also known as: Keytruda

Pembrolizumab + Palliative Radiation Therapy

Radiation Therapy RADIATION

9 Gy X 3 (27 Gy in 3 fractions), or 4-6 Gy X 5 (20-30 Gy in 5 fractions).

Pembrolizumab + Palliative Radiation Therapy

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 Merkel Cell Carcinoma.
• Patients are eligible if they have received no more than 3 prior systemic treatments, inclusive of systemic adjuvant therapy. This includes previously untreated patients.
• Subjects with brain metastases and/or carcinomatous meningitis are eligible providing they are neurologically stable (if systemic steroids are required, subjects should be stable on the lowest clinically effective dose, as steroids may interfere with the activity of immunotherapy if administered at the time of the first Anti-PD-1/PD-L1 dose.)
• Availability of tumor tissue (fresh or archival) for central pathology review.
• Must be at least 14 days since treatment with chemotherapy, biochemotherapy, surgery, or immunotherapy, and recovered (baseline or residual Grade 1 toxicity) from any clinically significant toxicity experienced during treatment before the first dose of pembrolizumab therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of ≥ 16 weeks.
• Subjects must have measurable disease according to RECIST v1.1, and have baseline (screening/baseline) radiographic images, (e.g. CT, Positron emission tomography (PET)/CT or MRI brain, chest, abdomen, pelvis, to be determined by the attending physician) within 4 weeks of confirmation of eligibility and within 6 weeks before the initiation of pembrolizumab therapy.
• Required values for initial laboratory tests:
• White blood cells (WBC): ≥ 2000/µL (\~ 2 x 109/L)
• Absolute Neutrophil Count (ANC): ≥ 1000/µL (\~ 1 x 109/L) Platelets: ≥ 50 x 103/µL (\~ 50 x 109/L)
• Hemoglobin: ≥ 8 g/dL
• Calculated creatinine clearance greater than 30 mL/min
• Aspartate transaminase(AST)/alanine transaminase (ALT): Less than 2.5 x upper limit of normal (ULN) for subjects without liver metastasis, less than 5 times ULN for liver metastases
• Bilirubin: less than 3.0 x ULN (except for subjects with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)

You may not qualify if:

• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 26 weeks after the last dose of investigational product.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or before investigational product administration.
• Subjects on any other systemic therapy for cancer, including any other experimental treatment within 2 weeks of scheduled first dose of pembrolizumab.
• A history of AEs with prior IL-2 or Interferon will not preclude subjects from entering the current study.
• Autoimmune disease: Poorly controlled autoimmune disease is excluded. Well controlled autoimmune disease (e.g. well controlled RA) will be assessed by the study team and a decision made regarding eligibility based on the degree of immunosuppression and severity of symptoms.
• Any subject who has a life-threatening condition that requires high-dose immunosuppressant(s). Steroid doses greater than 20 mg/day will exclude the patient from participation in the trial.
• Presence of known hepatitis B or hepatitis C infection, regardless of control on antiviral therapy.
• Subjects who have another active, concurrent, malignant disease are not eligible, with the exception of subjects with adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or other cancers that are in remission/not measurable. Patients will be excluded if they have any known additional malignancy that requires active treatment while on treatment for Merkel Cell Carcinoma.
• Bilirubin/total bilirubin 3 or more X ULN unless conjugated bilirubin is less than or equal to the ULN.
• Evidence of symptomatic interstitial lung disease or symptomatic active, noninfectious pneumonitis.
• Participants with impaired cardiac function or clinically significant cardiac disease such as unstable angina/uncompensated heart failure, uncontrolled symptomatic arrhythmia.
• Active autoimmune disease requiring systemic T-cell immunosuppression.
• Known hypersensitivity to another monoclonal antibody, which cannot be controlled with standard measures (e.g. antihistamines and corticosteroids).
• Any condition that would, in the investigator's judgment, interfere with full participation in the study.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

pembrolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Susan J Knox, Associate Professor of Radiation Oncology
• Organization: Stanford University

sknox@stanford.edu

650-725-2720

Study Officials

• Susan J Knox, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

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: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiation Oncology

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 17, 2019
• Study Start: July 24, 2019
• Primary Completion: November 16, 2020
• Study Completion: January 20, 2021
• Last Updated: August 9, 2021
• Results First Posted: August 9, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)