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Aldesleukin Imaging in Viewing Tumor Growth in Patients With Stage IV Melanoma Receiving Ipilimumab or Pembrolizumab Therapy

Primary Purpose

Stage IV Skin Melanoma

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Laboratory Biomarker Analysis

Radionuclide Imaging

Technetium Tc 99 Hydrazinonicotinamide-Tricine-linked Interleukin-2

About this trial

This is an interventional diagnostic trial for Stage IV Skin Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Pathologic proof of stage IV melanoma (pathology report confirmation) with plans to initiate therapy with ipilimumab or pembrolizumab according to Food and Drug Administration (FDA) approved guidelines, with multiple lesions such that
- Two of these lesions are in the same organ and at least one of these two lesions is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using either intravenous (IV) contrast enhanced computed tomography (CT) or CT component of positron emission tomography (PET)/CT OR
- Three of these lesions are in different organs and at least one of these 3 lesions is measurable by RECIST 1.1 using either IV contrast enhanced CT or CT component of PET/CT
Patient eligible for and will be receiving ipilimumab or pembrolizumab as standard of care therapy
Absolute neutrophil count (ANC) >= 1500 mL
Hemoglobin (Hgb) > 10 g/dL
Platelets (PLT) >= 50,000 mL
Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
Alkaline phosphatase =< 3 x ULN; up to 5 x allowed for patients with liver metastases
Ability to provide informed consent
Willingness to return to Mayo Clinic Rochester for follow-up
Life expectancy >= 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
For women of childbearing potential, a negative serum pregnancy test =< 7 days prior to registration
Willingness to participate in mandatory imaging studies as well as provide mandatory blood samples for correlative research
Tumor accessible for biopsy

Exclusion Criteria:

Uncontrolled or current infection
Known allergy to 99mTc-HYNIC-IL2 or components
Any of the following prior therapies with interval since most recent treatment:
- Chemotherapy =< 3 weeks prior to registration
- Biologic therapy =< 3 weeks prior to registration
- Radiation therapy =< 3 weeks prior to registration
Failure to recover from side effects of prior chemotherapy or surgery
Any of the following:
- Pregnant women
- Nursing women
- Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort I (scintigraphy prior to immunotherapy and 12 weeks)

Cohort II (scintograpy prior to immunotherapy, 3-4, 12 weeks)

Arm Description

Patients undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy prior to receiving ipilimumab or pembrolizumab and at 12 weeks.

Patients undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy prior to receiving ipilimumab or pembrolizumab, at 3-4 weeks, and at 12 weeks.

Outcomes

Primary Outcome Measures

Proportion of patients who develop scintigraphy limiting toxicities (SLTs)

SLTs include grade 2+ allergic reaction, grade 3+ anaphylaxis, grade 2+ injection site reaction, or grade 3+ non-hematologic toxicity (not attributed to immunotherapy treatment/progression or a co-morbid condition). A 95% binomial confidence interval of the proportion of patients who develop a grade 2+ allergic reaction, grade 3+ anaphylaxis, or grade 2+ injection site reaction will be constructed.

Secondary Outcome Measures

Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.

Target-to-background (T/B) ratio as determined by technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy

Spearman rank correlation coefficients will be used to examine the association between T/B ratio and the pre-treatment tumor biomarkers. Spearman rank correlation coefficients will be used to examine the association between changes in T/B ratio, changes in TIL percentages, and changes in peripheral blood concentrations of T, B, and NK cell subsets.

TIL invasion as determined by technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy

Relationship between TIL invasion, tumor burden, tumor based biomarkers, and peripheral blood biomarkers will be assessed.

Full Information

NCT ID

NCT01789827

First Posted

February 8, 2013

Last Updated

August 1, 2019

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01789827

Brief Title

Aldesleukin Imaging in Viewing Tumor Growth in Patients With Stage IV Melanoma Receiving Ipilimumab or Pembrolizumab Therapy

Official Title

Interleukin-2 Imaging as a Guide to Cancer Immunotherapy (Ipilimumab or Pembrolizumab) in Advanced Melanoma: A Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

March 2014 (Actual)

Primary Completion Date

June 27, 2018 (Actual)

Study Completion Date

June 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This pilot clinical trial studies aldesleukin imaging in viewing tumor growth in patients with stage IV melanoma receiving ipilimumab or pembrolizumab therapy. Diagnostic procedures, such as single-photon emission computed tomography (SPECT), uses radioactive drugs and a scanner to make detailed pictures of areas inside the body and may be a less invasive way to check for stage IV melanoma. Radioactive drugs, such as technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2, carry radiation directly to cancer cells and may be able to differentiate between tumor growth due to inflammation versus tumor progression in patients with stage IV melanoma receiving therapy.

Detailed Description

PRIMARY OBJECTIVES: I. Feasibility/biodistribution of 99mTc-HYNIC-IL2 (technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin 2) scintigraphy in patients with metastatic melanoma undergoing immunotherapy with either ipilimumab (commercial source) or pembrolizumab. SECONDARY OBJECTIVES: I. Correlation of tumor infiltrating lymphocyte (TIL) invasion (scintigraphy/histology) with tumor burden; and description of any clinical side effects associated with imaging. TERTIARY OBJECTIVES: I. Correlation of TIL invasion assessed by 99mTc-HYNIC-IL2 scintigraphy vs. histology (total and subsets of TIL), as well as screen for peripheral blood correlates. OUTLINE: Patients are assigned to 1 of 2 groups. COHORT I: Patients undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy prior to receiving ipilimumab or pembrolizumab and at 12 weeks. COHORT II: Patients undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy prior to receiving ipilimumab or pembrolizumab, at 3-4 weeks, and at 12 weeks. After completion of study treatment, patients are followed up at 30-45 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stage IV Skin Melanoma

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort I (scintigraphy prior to immunotherapy and 12 weeks)

Arm Type

Experimental

Arm Description

Patients undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy prior to receiving ipilimumab or pembrolizumab and at 12 weeks.

Arm Title

Cohort II (scintograpy prior to immunotherapy, 3-4, 12 weeks)

Arm Type

Experimental

Arm Description

Patients undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy prior to receiving ipilimumab or pembrolizumab, at 3-4 weeks, and at 12 weeks.

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Procedure

Intervention Name(s)

Radionuclide Imaging

Other Intervention Name(s)

nuclear medicine scan, radioimaging, Radionuclide Scanning, Scan, SCINTIGRAPHY

Intervention Description

Undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphies

Intervention Type

Biological

Intervention Name(s)

Technetium Tc 99 Hydrazinonicotinamide-Tricine-linked Interleukin-2

Other Intervention Name(s)

99mTc-HYNIC-IL2

Intervention Description

Undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphies

Primary Outcome Measure Information:

Title

Proportion of patients who develop scintigraphy limiting toxicities (SLTs)

Description

Time Frame

Up to 12 weeks

Secondary Outcome Measure Information:

Title

Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Description

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.

Time Frame

Up to 30-45 days after study discontinuation

Title

Target-to-background (T/B) ratio as determined by technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy

Description

Time Frame

Up to 12 weeks

Title

TIL invasion as determined by technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy

Description

Relationship between TIL invasion, tumor burden, tumor based biomarkers, and peripheral blood biomarkers will be assessed.

Time Frame

Up to 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Pathologic proof of stage IV melanoma (pathology report confirmation) with plans to initiate therapy with ipilimumab or pembrolizumab according to Food and Drug Administration (FDA) approved guidelines, with multiple lesions such that Two of these lesions are in the same organ and at least one of these two lesions is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using either intravenous (IV) contrast enhanced computed tomography (CT) or CT component of positron emission tomography (PET)/CT OR Three of these lesions are in different organs and at least one of these 3 lesions is measurable by RECIST 1.1 using either IV contrast enhanced CT or CT component of PET/CT Patient eligible for and will be receiving ipilimumab or pembrolizumab as standard of care therapy Absolute neutrophil count (ANC) >= 1500 mL Hemoglobin (Hgb) > 10 g/dL Platelets (PLT) >= 50,000 mL Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) Alkaline phosphatase =< 3 x ULN; up to 5 x allowed for patients with liver metastases Ability to provide informed consent Willingness to return to Mayo Clinic Rochester for follow-up Life expectancy >= 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 For women of childbearing potential, a negative serum pregnancy test =< 7 days prior to registration Willingness to participate in mandatory imaging studies as well as provide mandatory blood samples for correlative research Tumor accessible for biopsy Exclusion Criteria: Uncontrolled or current infection Known allergy to 99mTc-HYNIC-IL2 or components Any of the following prior therapies with interval since most recent treatment: Chemotherapy =< 3 weeks prior to registration Biologic therapy =< 3 weeks prior to registration Radiation therapy =< 3 weeks prior to registration Failure to recover from side effects of prior chemotherapy or surgery Any of the following: Pregnant women Nursing women Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Svetomir Markovic

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Aldesleukin Imaging in Viewing Tumor Growth in Patients With Stage IV Melanoma Receiving Ipilimumab or Pembrolizumab Therapy

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