177Lu-PSMA (177Lu-PNT2002) in PSMA-Positive Adenoid Cystic Carcinoma

March 20, 2024 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

A Phase 2, Single-Arm, Multi-center Study of 177Lu-PSMA (177Lu-PNT2002) in Patients With PSMA-Positive Adenoid Cystic Carcinoma

This is a single arm trial with one Cohort for people with recurrent or metastatic adenoid cystic carcinoma that cannot be treated with surgery. 10 participants will be enrolled in Cohort 1 at Johns Hopkins and will undergo DCFPyL PET/CT and 177Lu-PSMA dosimetry imaging only (single tracer dose). A feasibility analysis of dosimetry will be performed after meeting the accrual goal of Cohort 1 to determine if the study will proceed into Cohort 2.

If Cohort 2 proceeds, based on the dosimetry analysis, the major requirements of the study are to undergo treatment with 177Lu-PNT2002, have bloodwork, physical exams, and imaging done at study-specific time points, and to answer questionnaires. Patients will be in the study for about two years after enrolling.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Malignant salivary gland tumors account for approximately 3% to 5% of all head and neck cancers with approximately 0.4 to 2.6 cases per 100,000 people. Most patients present in the sixth to seventh decade of life. Adenoid cystic carcinoma (ACC) accounts for about 10% of all tumors of the salivary glands, often arises from the minor and major salivary glands but can also involve lacrimal and ceruminous glands, as well as other sites in the head and neck (nasal and paranasal sinuses, trachea, and larynx). Anatomically, ACC originates from the intercalated duct region and proliferates in three distinct architectural patterns: tubular, cribriform, and solid.

In the setting of recurrent and metastatic (R/M) ACC, first-line options include single-agent vinorelbine or mitoxantrone, or cyclophosphamide plus doxorubicin plus cisplatin (CAP). Overall response rates (ORR) are usually less than 15%. There are no effective second line options. While epidermal growth factor receptor (EGFR) has been shown to be overexpressed in some ACC, none of the phase II clinical trials of single agent cetuximab, gefitinib, or lapatinib demonstrated an objective response. Many cases of ACC also express the c-kit protein, however, use of single agent imatinib in patients with c-kit expression confirmed by immunohistochemistry (IHC) failed to produce an objective response. Phase II single agent sunitinib exhibited no objective response. Median progression free survival (PFS) of these phase II trials ranged from 3.5 months to 7.2 months. Ultimately, most patients with R/M ACC die from cancer, highlighting the need for effective therapies.

The investigators aim to examine and analyze PSMA-PET uptake in ACC to establish whether it is correlated to absorbed tumor dose and objective response in Cohort 1 participants.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologic confirmation of ACC (primary or metastatic tumor). Central review not required but local pathology review required (at Johns Hopkins or Stanford).
  • Patients must have recurrent or metastatic ACC with measurable disease per RECIST 1.1, not amenable to definitive surgery or radiotherapy.
  • Patients must have at least 1 lesion positive on PSMA-PET, as defined by standard uptake value (SUV) ratio of tumor to liver greater than one.
  • Patient can have any or no prior systemic therapies.
  • At least 28 days must have elapsed between last anti-cancer treatment administration and the initiation of study treatment, or at least 5 half-lives of the prior systemic therapy must have elapsed (whichever is shorter).
  • Patient must have resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤ 2.
  • Patient must be ≥ 18 years of age.
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

For female patients with childbearing potential or male patients with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 6 months from receiving the last dose of 177Lu-PSMA. Female patients with childbearing potential will undergo a urine pregnancy test. Pregnant female participants are excluded.

  • Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Spinal cord compression or impending spinal cord compression.
  • Suspected pulmonary and/or liver metastases (greater >10 mm in largest axis).
  • Unable to lie flat during or tolerate PET/CT.
  • Refusal to sign informed consent.
  • Any medical comorbidities that might preclude safe participation in the study.

Additional inclusion criteria only relevant if Cohort 2 participants enrolled:

  • Adequate bone marrow reserve and organ function as demonstrated by complete blood count and chemistry panel completed within the prior 28 days demonstrating:

    1. Platelet count of >100 x109/L
    2. White blood cell (WBC) count > 3,000/mL
    3. Neutrophil count of > 1,500/mL
    4. Hemoglobin ≥ 10 g/dL
    5. Estimated glomerular filtration rate (eGFR) > 50 mL/min based upon Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Due to safety concerns relating to renal clearance and toxicity of 177Lu-PSMA, patients with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only patients with non-obstructive pathology will be included in the study.
    6. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤5 x upper limit of normal (ULN), total bilirubin < 3 x ULN
    7. Total bilirubin < 3 x ULN (except if confirmed history of Gilbert's disease)
    8. Serum albumin > 30 g/L

Additional exclusion criteria only relevant if Cohort 2 participants enrolled:

  • Inadequate bone marrow reserve and organ function as detailed in eligibility criteria.
  • Patient is participating in a concurrent investigative treatment protocol involving radiotherapy, surgery, or systemic anti-cancer agents.
  • Patient receiving any other investigational agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SPECT CT Dosimetry
Absorbed dose in tumor and normal organs will by measured using SPECT/CT dosimetry in Cohort 1.
Drug: 177Lu-PNT2002

10 patients will undergo DCFPyL PET/CT and 177Lu-PSMA dosimetry imaging only (single tracer dose).

If opened, Cohort 2 patients will receive 4 cycles, every 8 weeks of 177Lu-PSMA infusion. Other procedures during treatment and follow up may include: physical exam, CT/MRI, PSMA-PET, blood draws, adverse event assessment, and completion of questionnaires.

Other Names:
  • 177Lu PSMA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absorbed dose in tumor and normal organs
Time Frame: One dose during one day
Objective is to measure absorbed dose in tumor and normal organs using SPECT/CT dosimetry (Cohort 1)
One dose during one day
Objective response rate (ORR) by RECIST 1.1 measured in patients treated with 177Lu-PSMA for recurrent and metastatic ACC.
Time Frame: Pre-treatment, 6 months post treatment
Only relevant for Cohort 2 patients: Measure response rate (ORR) by RECIST 1.1 in participants treated with 177Lu-PSMA for recurrent and metastatic ACC.
Pre-treatment, 6 months post treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stability of Disease: Proportion of patients with Stable Disease
Time Frame: 6 months post treatment
Cohort 2 participants only. Stability of disease at 6 months is defined as the proportion of patients with SD as assessed per RECIST 1.1 at 6 months after the last cycle of treatment. This 6-month post treatment time point will vary based on the total number of cycles the patient receives.
6 months post treatment
Duration of Response
Time Frame: 24 months after Day 1 of treatment

Cohort 2 participants only. Objective response will be defined as evidence of CR, PR, or stable disease. The duration of response will be measured from the start of treatment until the criteria for progression are met.

Duration of CR or PR: The duration of response (DoR) of CR or PR will be recorded from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that current or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Duration of Stable Disease: Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started.
24 months after Day 1 of treatment
Xerostomia questionnaire (XQ) score
Time Frame: 24 months after Day 1 of treatment
Only relevant if able to enroll Cohort 2 patients: Xerostomia questionnaire (XQ) will be completed by patients at baseline, prior to each dose of 177Lu-PSMA, at end of treatment, and at follow up visits. XQ measures severity of radiation-induced xerostomia and patient reported quality of life. 8 question total:4 on dryness while eating/chewing, 4 on dryness when not eating/chewing. 0-10 (higher scores=severe dryness/discomfort). Composite Scores range from 0 (no xerostomia) -100 (highest level of xerostomia).
24 months after Day 1 of treatment
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43)
Time Frame: 24 months after Day 1 of treatment
Only relevant if able to enroll Cohort 2 patients: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43) will be completed by patients at baseline, prior to each dose of 177Lu-PSMA, at end of treatment, and at follow up visits. Answers given according to a 4-point Likert scale, and then transformed so that 0% indicated least symptoms, and 100% most symptoms.
24 months after Day 1 of treatment
Progression Free Survival
Time Frame: 24 months after Day 1, Cycle 1 of treatment (each cycle is 8 weeks)
Only relevant if able to enroll Cohort 2 patients: The distribution of progression free survival will be plotted using the Kaplan Meier method and median values will be estimated and reported with 95% CIs
24 months after Day 1, Cycle 1 of treatment (each cycle is 8 weeks)
Overall Survival
Time Frame: 24 months after Day 1, Cycle 1 of treatment (each cycle is 8 weeks)
Only relevant if able to enroll Cohort 2 patients: The distribution of overall survival will be plotted using the Kaplan Meier method and median values will be estimated and reported with 95% CIs
24 months after Day 1, Cycle 1 of treatment (each cycle is 8 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Adenoid Cystic Carcinoma Research Foundation
Progenics Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Ana Kiess, MD, PhD, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

December 1, 2030

Study Completion (Estimated)

December 1, 2035

Study Registration Dates

First Submitted

February 13, 2024

First Submitted That Met QC Criteria

March 14, 2024

First Posted (Actual)

March 21, 2024

Study Record Updates

Last Update Posted (Actual)

March 22, 2024

Last Update Submitted That Met QC Criteria

March 20, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00347750

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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