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Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer

Primary Purpose

Breast Adenocarcinoma, Metastatic Breast Carcinoma, Recurrent Breast Carcinoma

Status
Suspended
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Belinostat
Carfilzomib
Copanlisib Hydrochloride
Daratumumab
Fludeoxyglucose F-18
Gemcitabine Hydrochloride
Laboratory Biomarker Analysis
Nivolumab
Obinutuzumab
Pembrolizumab
Positron Emission Tomography
Rituximab
Romidepsin
Saline
Trastuzumab
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Adenocarcinoma

Eligibility Criteria

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

Inclusion Criteria:

  • Age >= 18 years

  • Histologically proven of relapsed or refractory

    • Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) nodal or extranodal mass OR
    • Cutaneous T-cell lymphoma (CTCL) including mycosis fungoides (MF), as well as transformed MF OR

    • Breast adenocarcinoma with nodal or cutaneous metastases (stage 4)

      • NOTE: Patients must be refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition
      • NOTE: The patient must not be a candidate for any curative therapy or any known life-prolonging therapy

  • Cohort I: For nodal/extranodal mass, presence of lesions that are amenable for injections as determined by interventional radiology

    • NOTE: Nodal or extranodal mass must be palpable and easily accessible; masses such as mediastinum, retroperitoneum, within solid organs, spinal sites, central nervous system (CNS) sites, etc., are NOT allowed

  • Measurable disease:

    • For nodal or extranodal disease (lymphoma or breast): must have at least 2 lesions that are >= 20 mm (2.0 cm) in the longest diameter by physical exam and/or on cross-sectional imaging and measurable in two perpendicular dimensions per computed tomography PET-computed tomography (CT); For Cohort I, the lesions must be amenable to intralesional injections as determined by interventional radiology (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)
    • For cutaneous lesions (lymphoma or breast): at least two visible, non-infected skin lesions that are greater than 1 cm and are amenable to intralesional injection as determined by investigator
  • Candidate for further therapy and able to wait 7 days prior to start of next systemic therapy
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
  • Platelet count >= 50,000/mm^3 (obtained =< 14 days prior to registration)
  • International normalized ratio (INR)/prothrombin time (PT) =< 1.5 (obtained =< 14 days prior to registration)
  • Negative serum or urine pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
  • Provide written informed consent
  • Willing to return to enrolling institution for follow-up
  • Willing to provide tissue samples for correlative research purposes

Exclusion Criteria:

  • Any of the following:

    • Pregnant persons
    • Nursing persons
    • Persons of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Systemic corticosteroids between pre-PET and post-PET evaluation and biopsy

  • Prohibited treatments and or therapies

    • Autologous stem cell transplant (ASCT) =< 12 weeks prior to registration
    • Prior chemotherapy =< 2 weeks prior to registration
    • Prior treatment with nitrosureas =< 4 weeks prior to registration
    • Therapeutic anticancer antibodies =< 2 weeks prior to registration
    • Radio- or toxin immunoconjugates =< 4 weeks prior to registration
    • Radiation therapy to the injected area =< 2 weeks prior to registration
    • Major surgery =< 2 weeks prior to registration
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

  • Requires anticoagulation that cannot be discontinued prior to biopsy

    • Note: Exception if able to hold antiplatelet agents 7 days prior to the injections and biopsy
    • NOTE: Low molecular weight heparin (LMWH) will be allowed for bridging if on warfarin
    • NOTE: Heparin for line patency without detectable lab abnormalities for coagulation will be allowed

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (FDG-PET, direct tumor microinjection)

Arm Description

Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.

Outcomes

Primary Outcome Measures

Incidence of drug sensitivity as measured by injection site skin reaction
Skin reactions will be assessed using the Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) and will consist of any grade 3 or higher treatment-related pain, skin or subcutaneous tissue disorders. Incidence rates of skin reactions will be estimated by the number of patients with reactions divided by the total number of evaluable patients per disease type. Exact binomial 95% confidence intervals for the true incidence rate will be calculated.

Secondary Outcome Measures

Feasibility
For Cohort I (Arms A & B) and Cohort II (Arm D): The study will be determined to be feasible if at least 70% of the enrolled patients complete the injection and response evaluation. The feasibility rate will be estimated by the number of patients completed divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true feasibility rate will be calculated. For Cohort II (Arm C): The feasibility rate will be evaluated for the device regarding whether the device will be able to target the affected lymph nodes in at least 50% of the time. The feasibility rate will be estimated by the number of patients completed divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true feasibility rate will be calculated.
Nodal disease response rate
Defined as a decrease in standardized uptake value (SUV) uptake by 25% at site of injection. Will be estimated by the number of injection sites with responses divided by the total number of injected sites. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Cutaneous response rate based upon the modified Severity Weighted Assessment Tool score
Will be estimated by the number of injection sites with responses divided by the total number of injected sites. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Incidence of adverse events
Will be evaluated using the CTEP active version of the CTCAE. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.

Full Information

First Posted
February 8, 2018
Last Updated
September 11, 2023
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT03432741
Brief Title
Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer
Official Title
Pilot Safety and Feasibility Study of an In Vivo Sensitivity Screen Using a Direct Tumor Microinjection Technique and FDG-PET
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Suspended
Why Stopped
funding - sponsor filing of Chapter 11 bankruptcy
Study Start Date
March 27, 2018 (Actual)
Primary Completion Date
April 1, 2025 (Anticipated)
Study Completion Date
May 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot phase I trial studies the side effects of direct tumor microinjection and fludeoxyglucose F-18 positron emission tomography (FDG-PET) in testing drug sensitivity in patients with non-Hodgkin lymphoma, Hodgkin lymphoma, or stage IV breast cancer that has returned after a period of improvement or does not respond to treatment. Injecting tiny amounts of anti-cancer drugs directly into tumors on the skin or in lymph nodes and diagnostic procedures, such as FDG-PET, may help to show which drugs work better in treating patients with non-Hodgkin lymphoma, Hodgkin lymphoma, or breast cancer.
Detailed Description
PRIMARY OBJECTIVE: I. To assess the safety of in vivo in host drug sensitivity testing in patients with breast cancer and patients with lymphoma (nodal, extranodal masses, or cutaneous lesions). SECONDARY OBJECTIVES: I. To assess the feasibility of in vivo in host drug sensitivity testing in this patient population. II. To identify targeted therapies with potential activity in relapsed lymphoma and metastatic breast cancer. III. To evaluate the adverse event profile within each patient population. CORRELATIVE OBJECTIVES: I. To assess for apoptosis in response to intratumoral injection using known biomarkers (e.g., by morphology, Ki-67, caspace-3 assay as a marker of early apoptosis). II. To evaluate intratumoral biomarkers, intratumoral cell populations, and distribution, identify potential biomarkers that correlate with response to therapy based on individual therapies. OUTLINE: Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy. After completion of study treatment, patients are followed up at 3 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Adenocarcinoma, Metastatic Breast Carcinoma, Recurrent Breast Carcinoma, Recurrent Hodgkin Lymphoma, Recurrent Mycosis Fungoides, Recurrent Non-Hodgkin Lymphoma, Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Refractory Breast Carcinoma, Refractory Hodgkin Lymphoma, Refractory Mycosis Fungoides, Refractory Nodal Marginal Zone Lymphoma, Refractory Non-Hodgkin Lymphoma, Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Stage IV Breast Cancer AJCC v6 and v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (FDG-PET, direct tumor microinjection)
Arm Type
Experimental
Arm Description
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
Intervention Type
Drug
Intervention Name(s)
Belinostat
Other Intervention Name(s)
Beleodaq, PXD 101, PXD101
Intervention Description
Given intralesionally
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis, PR-171
Intervention Description
Given intralesionally
Intervention Type
Drug
Intervention Name(s)
Copanlisib Hydrochloride
Other Intervention Name(s)
5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 Dihydrochloride, Copanlisib Dihydrochloride
Intervention Description
Given intralesionally
Intervention Type
Biological
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414
Intervention Description
Given intralesionally
Intervention Type
Drug
Intervention Name(s)
Fludeoxyglucose F-18
Other Intervention Name(s)
18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18
Intervention Description
Undergo FDG-PET
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011
Intervention Description
Given intralesionally
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given intralesionally
Intervention Type
Biological
Intervention Name(s)
Obinutuzumab
Other Intervention Name(s)
Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759
Intervention Description
Given intralesionally
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Lambrolizumab, MK-3475, SCH 900475
Intervention Description
Given intralesionally
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Intervention Description
Undergo FDG-PET
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima
Intervention Description
Given intralesionally
Intervention Type
Drug
Intervention Name(s)
Romidepsin
Other Intervention Name(s)
Antibiotic FR 901228, Depsipeptide, FK228, FR901228, Istodax, N-[(3S,4E)-3-Hydroxy-7-mercapto-1-oxo-4-heptenyl]-D-valyl-D-cysteinyl-(2Z)-2-amino-2-butenoyl-L-valine, (4->1) Lactone, Cyclic
Intervention Description
Given intralesionally
Intervention Type
Other
Intervention Name(s)
Saline
Other Intervention Name(s)
ISOTONIC SODIUM CHLORIDE SOLUTION, Sodium Chloride 0.9%
Intervention Description
Given intralesionally
Intervention Type
Biological
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
ABP 980, ALT02, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Herzuma, Kanjinti, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, Ogivri, Ontruzant, PF-05280014, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-qyyp, Trazimera
Intervention Description
Given intralesionally
Primary Outcome Measure Information:
Title
Incidence of drug sensitivity as measured by injection site skin reaction
Description
Skin reactions will be assessed using the Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) and will consist of any grade 3 or higher treatment-related pain, skin or subcutaneous tissue disorders. Incidence rates of skin reactions will be estimated by the number of patients with reactions divided by the total number of evaluable patients per disease type. Exact binomial 95% confidence intervals for the true incidence rate will be calculated.
Time Frame
Up to 3 months
Secondary Outcome Measure Information:
Title
Feasibility
Description
For Cohort I (Arms A & B) and Cohort II (Arm D): The study will be determined to be feasible if at least 70% of the enrolled patients complete the injection and response evaluation. The feasibility rate will be estimated by the number of patients completed divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true feasibility rate will be calculated. For Cohort II (Arm C): The feasibility rate will be evaluated for the device regarding whether the device will be able to target the affected lymph nodes in at least 50% of the time. The feasibility rate will be estimated by the number of patients completed divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true feasibility rate will be calculated.
Time Frame
Up to 3 months
Title
Nodal disease response rate
Description
Defined as a decrease in standardized uptake value (SUV) uptake by 25% at site of injection. Will be estimated by the number of injection sites with responses divided by the total number of injected sites. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Time Frame
Up to 5 days post injection
Title
Cutaneous response rate based upon the modified Severity Weighted Assessment Tool score
Description
Will be estimated by the number of injection sites with responses divided by the total number of injected sites. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Time Frame
Up to 7 days post injection
Title
Incidence of adverse events
Description
Will be evaluated using the CTEP active version of the CTCAE. 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 3 months
Other Pre-specified Outcome Measures:
Title
Apoptosis in response to intratumoral injection
Description
Will assess using morphology (evidence of necrosis), measurement by immunohistochemistry of Ki67 (a marker of cell proliferation) and cleaved Caspace-3.
Time Frame
Up to 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >= 18 years Histologically proven of relapsed or refractory Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) nodal or extranodal mass OR Cutaneous T-cell lymphoma (CTCL) including mycosis fungoides (MF), as well as transformed MF OR Breast adenocarcinoma with nodal or cutaneous metastases (stage 4) NOTE: Patients must be refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition NOTE: The patient must not be a candidate for any curative therapy or any known life-prolonging therapy Cohort I: For nodal/extranodal mass, presence of lesions that are amenable for injections as determined by interventional radiology NOTE: Nodal or extranodal mass must be palpable and easily accessible; masses such as mediastinum, retroperitoneum, within solid organs, spinal sites, central nervous system (CNS) sites, etc., are NOT allowed Measurable disease: For nodal or extranodal disease (lymphoma or breast): must have at least 2 lesions that are >= 20 mm (2.0 cm) in the longest diameter by physical exam and/or on cross-sectional imaging and measurable in two perpendicular dimensions per computed tomography PET-computed tomography (CT); For Cohort I, the lesions must be amenable to intralesional injections as determined by interventional radiology (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures) For cutaneous lesions (lymphoma or breast): at least two visible, non-infected skin lesions that are greater than 1 cm and are amenable to intralesional injection as determined by investigator Candidate for further therapy and able to wait 7 days prior to start of next systemic therapy Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration) Platelet count >= 50,000/mm^3 (obtained =< 14 days prior to registration) International normalized ratio (INR)/prothrombin time (PT) =< 1.5 (obtained =< 14 days prior to registration) Negative serum or urine pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only Provide written informed consent Willing to return to enrolling institution for follow-up Willing to provide tissue samples for correlative research purposes Exclusion Criteria: Any of the following: Pregnant persons Nursing persons Persons of childbearing potential who are unwilling to employ adequate contraception Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Systemic corticosteroids between pre-PET and post-PET evaluation and biopsy Prohibited treatments and or therapies Autologous stem cell transplant (ASCT) =< 12 weeks prior to registration Prior chemotherapy =< 2 weeks prior to registration Prior treatment with nitrosureas =< 4 weeks prior to registration Therapeutic anticancer antibodies =< 2 weeks prior to registration Radio- or toxin immunoconjugates =< 4 weeks prior to registration Radiation therapy to the injected area =< 2 weeks prior to registration Major surgery =< 2 weeks prior to registration Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm Requires anticoagulation that cannot be discontinued prior to biopsy Note: Exception if able to hold antiplatelet agents 7 days prior to the injections and biopsy NOTE: Low molecular weight heparin (LMWH) will be allowed for bridging if on warfarin NOTE: Heparin for line patency without detectable lab abnormalities for coagulation will be allowed
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Grzegorz S. Nowakowski, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer

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