Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

NCT03087019 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-609
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying immunotherapy with or without radiation therapy as a possible treatment for adenoid cystic carcinoma. The immunotherapy involved in this study is:

• Pembrolizumab (MK-3475 or KEYTRUDA).

Conditions

Adenoid Cystic Carcinoma

Keywords

adenoid cystic carcinoma

Outcome Measures

Primary Outcomes (1)

• Patients Demonstrating Objective Response In Non-Irradiated Lesions (Tumor Size on Scans)

  Objective response will be assessed in non-irradiated lesions among all eligible and treated patients pursuing RECIST 1.1. Per RECIST guidelines for target lesions, Complete Response (CR): disappearance of all target lesions; Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): \>20% increase in sum of the longest diameter (LD) of measured lesions, referencing the smallest sum LD, or new lesions; Stable Disease (SD): neither PR nor PD. Objective response refers to tumor shrinkage at least qualifying as PR.

  2 years

Secondary Outcomes (5)

• Progression Free Survival (Time From Randomization to Disease Progression or Death)

  2 years

• Overall Survival (Time From Randomization to Death)

  2 years

• Number of Participants With Complete Response (Absence of Non-irradiated Lesions on Scans)

  2 years

• Number of Participants With Partial Response (Tumor Size on Scans)

  2 years

• Number of Treatment-Emergent Adverse Events

  2 years

Study Arms (2)

Pembrolizumab + Radiation

EXPERIMENTAL

* Up to 5 metastatic lesions targeted with radiation * Over 5 fractions starting within 7 calendar days following the first dose of pembrolizumab * Pembrolizumab will be administered on day 1 of each 21day cycle * Pembrolizumab is delivered intravenously

Radiation: Radiation; Drug: Pembrolizumab

Pembrolizumab

EXPERIMENTAL

* Pembrolizumab will be administered on day 1 of each 21day cycle * Pembrolizumab is delivered intravenously

Drug: Pembrolizumab

Interventions

Radiation RADIATION

Standard use of radiation is administered

Pembrolizumab + Radiation

Pembrolizumab DRUG

Pembrolizumab is designed to restore the natural ability of the immune system to recognize and target cancer cells.

Also known as: Keytruda

Pembrolizumab; Pembrolizumab + Radiation

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed adenoid cystic carcinoma with evidence of recurrent or metastatic disease not amenable to potentially curative surgery or radiotherapy.
• Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline and after 2 cycles of pembrolizumab. Participants can be exempt if archival tumor tissue has been collected within 12 months of study enrollment that the Principal Investigator deems it appropriate/sufficient for analysis on this protocol. Biopsy of a lesion outside of the potential radiation treatment field is preferred to maintain consistency across cohorts.
• Participants must have archival tissue from the primary tumor or metastases available for correlative studies. Either a paraffin block or twenty unstained slides are acceptable. If twenty slides are not available, a lesser amount may be acceptable after discussion with the Principal Investigator.
• Prior systemic therapy: At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (4 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤1 (or tolerable grade 2) or back to baseline (except for alopecia or neuropathy). Any number of prior therapies for recurrent/metastatic ACC are allowed, with the exception of previous treatment with PD-1 pathway inhibitors.
• Prior radiation therapy: At least 3 weeks must have elapsed from prior radiation therapy. The prior site of radiotherapy must be documented as reirradiation of the same site is not allowed in this protocol.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A).
• Participants must have documentation of a new or progressive lesion on a radiologic imaging study performed within 12 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 12 months prior to study enrollment. This assessment is performed by the treating investigator. Evidence of progression by RECIST criteria is not required.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
• Table 1 Adequate Organ Function Laboratory Values System Laboratory Value
• Hematological
• 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)
• Renal

You may not qualify if:

• Metastatic disease impinging on the spinal cord or threatening spinal cord compression. Patients that have had previous treatment of disease with impinging on the cord with either surgery or radiotherapy with clinical or radiographic evidence of response or stability are eligible.
• Surgical fixation of bone lesion to be irradiated is required and indicated to provide mechanical stability.
• Participant 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 four weeks prior to the first dose of trial treatment), have no evidence of new or enlarging brain metastases, and are not using steroids for the purposes of treating brain metastasis induced edema for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability, because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Prior treatment with PD-1 or PD-L1 inhibitor
• Concurrent administration of other cancer specific therapy or investigational agents during the course of this study is not allowed.
• Has a 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 trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• History of allergic reactions or hypersensitivity to pembrolizumab or any of its excipients.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• 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.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has 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.
• 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.
• Subjects who are 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. Pregnant women are excluded from this study because immunotherapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with immunotherapy, breastfeeding should be discontinued if the mother is treated on this protocol. Women who could potentially become pregnant while undergoing treatment on this protocol must be willing to use 2 methods of contraception.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02062, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Mahmood U, Bang A, Chen YH, Mak RH, Lorch JH, Hanna GJ, Nishino M, Manuszak C, Thrash EM, Severgnini M, Sanborn M, Sridharan V, Margalit DN, Tishler RB, Busse PM, Willers H, Mamon HJ, Yoo HJ, Pai SI, Wirth LJ, Haddad RI, Chau NG, Schoenfeld JD. A Randomized Phase 2 Study of Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma. Int J Radiat Oncol Biol Phys. 2021 Jan 1;109(1):134-144. doi: 10.1016/j.ijrobp.2020.08.018. Epub 2020 Aug 8.

  PMID: 32781104 DERIVED

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Interventions

Radiation; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Physical Phenomena

Results Point of Contact

• Title: Jonathan Schoenfeld, MD, MPH
• Organization: Dana-Farber Cancer Institute

jonathan_schoenfeld@dfci.harvard.edu

617-632-3591

Study Officials

• Jonathan Schoenfeld, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: March 22, 2017
• Study Start: April 25, 2017
• Primary Completion: August 4, 2020
• Study Completion: August 4, 2020
• Last Updated: October 14, 2022
• Results First Posted: April 22, 2021

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)