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Adenoid Cystic CarcinomaPhase 2NCT03087019

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

A Phase 2 study testing Radiation and Pembrolizumab in people with Adenoid Cystic Carcinoma, run by Dana-Farber Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Adenoid Cystic Carcinoma
What is being tested?
Radiation and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesUnited States
Study dates
25 Apr 2017to 4 Aug 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 have at least two RECIST v1.1 measurable non-CNS based lesions. Palliative radiation must be indicated for at least one of these lesions, and this lesion must be a candidate for radiation to a dose of 30 Gy of radiation over 5 fractions as deemed by a treating radiation oncologist. Documentation of volume and prescription isodose line will be collected. Re-irradiation of a previously treated lesion is not allowed. One lesion must be in a location where it will not be incorporated into the radiation fields so systemic response can be assessed. However, inclusion of patients with more than 10 measurable lesions is strongly discouraged and all patients must have life expectancy > 6 months.
  • 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.
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  • 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
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • Hepatic
  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
  • Albumin >2.5 mg/dL
  • Coagulation
  • International Normalized Ratio (INR) or Prothrombin Time (PT)
  • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Creatinine clearance should be calculated per institutional standard.
  • Baseline tumor measurements must be documented from tests within 28 days of study entry. Other non-laboratory tests must be performed within 28 days of study entry.
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 7 days 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 and male subjects of childbearing potential must agree to use an adequate method of contraception, as outlined in section 5.6, prior to study entry, for the duration of study participation, and 4 months after completion of pembrolizumab administration. Contraception is required starting with the first dose of study medication 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.
  • Be willing and able to provide written informed consent for the trial.

Who cannot join

  • 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.
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  • 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.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02062

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase II Trial of Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

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).
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational agent to learn whether it works in treating a specific disease. "Investigational" means that the drug is being studied.

Pembrolizumab (MK-3475 or KEYTRUDA) is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance (particles not typically found in your body such as bacteria or viruses). Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients. Pembrolizumab is designed to restore the natural ability of the immune system to recognize and target cancer cells.

The FDA recently granted approval to pembrolizumab as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma. Pembrolizumab has not been approved for treatment against adenoid cystic carcinoma.

This study is testing whether pembrolizumab with or without radiation is useful for patients with adenoid cystic carcinoma. Radiation therapy may be used to treat some ACC tumors that have spread to other parts of the body or recurred after surgery. Radiation therapy may affect the immune system to improve the efficacy of pembrolizumab

Keywords
adenoid cystic carcinoma
Medical subject headings
Carcinoma, Adenoid Cystic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RadiationRadiation

    Standard use of radiation is administered

  • PembrolizumabDrug

    Also called Keytruda

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

Study groups in NCT03087019
Study groupRoleWhat they receive
Pembrolizumab + RadiationExperimental* 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
Receives: Radiation: Radiation; Drug: Pembrolizumab
PembrolizumabExperimental* Pembrolizumab will be administered on day 1 of each 21day cycle * Pembrolizumab is delivered intravenously
Receives: Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years

Secondary outcomes (5)

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

    Progression-free survival is defined as the time from randomization to disease progression or death, whichever occurs first. Patients who are alive without disease progression will be censored at the date of last disease assessment. Progression-free survival will be evaluated using both RECIST 1.1 and immune-related response criteria (irRC), and both sets of results will be reported in each arm. Per RECIST criteria, progression is defined as a >=20% increase in the sum of the longest diameter of the measured lesions, referencing the smallest longest diameter sum, or the appearance of at least one new lesion.

    Measured: 2 years

  2. Overall Survival (Time From Randomization to Death)

    Overall survival is defined as the time from randomization to death or date last known alive. Overall survival will be evaluated using both RECIST 1.1 and immune-related response criteria (irRC), and both sets of results will be reported in each arm. will be evaluated using both RECIST 1.1 and immune-related response criteria (irRC), and both sets of results will be reported in each arm.

    Measured: 2 years

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

    Complete disappearance of all measurable non-irradiated lesions. All lymph nodes must be non-pathological in size (<10 mm short axis).

    Measured: 2 years

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

    At least a 30% decrease in the longest diameter valuated using RECIST 1.1.

    Measured: 2 years

  5. Number of Treatment-Emergent Adverse Events

    All patients who receive treatment, regardless of eligibility, will be evaluable for toxicity. Toxicity will be graded according to NCI CTCAE, Version 4.0. The proportions of patients with various toxicities will be reported by treatment arm.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2017
  2. Study start25 Apr 2017
  3. Primary completion4 Aug 2020
  4. Study completion4 Aug 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03087019
Sponsor's protocol ID
16-609
Status last verified
Oct 2022
First submitted
13 Mar 2017
Last updated
14 Oct 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32781104

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radiation and Pembrolizumab in people with Adenoid Cystic Carcinoma, run by Dana-Farber Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patients Demonstrating Objective Response In Non-Irradiated Lesions (Tumor Size on Scans) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03087019, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2022.

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