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

NCT03432741 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: MC1689NCI-2018-0014916-009337
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 3 months

Secondary Outcomes (4)

• Feasibility

  Up to 3 months

• Nodal disease response rate

  Up to 5 days post injection

• Cutaneous response rate based upon the modified Severity Weighted Assessment Tool score

  Up to 7 days post injection

• Incidence of adverse events

  Up to 3 months

Other Outcomes (1)

• Apoptosis in response to intratumoral injection

  Up to 3 months

Study Arms (1)

Treatment (FDG-PET, direct tumor microinjection)

EXPERIMENTAL

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.

Drug: Belinostat; Drug: Carfilzomib; Drug: Copanlisib Hydrochloride; Biological: Daratumumab; Drug: Fludeoxyglucose F-18; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Obinutuzumab; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Biological: Rituximab; Drug: Romidepsin; Other: Saline; Biological: Trastuzumab

Interventions

Belinostat DRUG

Given intralesionally

Also known as: Beleodaq, PXD 101, PXD101

Treatment (FDG-PET, direct tumor microinjection)

Carfilzomib DRUG

Given intralesionally

Also known as: Kyprolis, PR-171

Treatment (FDG-PET, direct tumor microinjection)

Copanlisib Hydrochloride DRUG

Given intralesionally

Also known as: 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

Treatment (FDG-PET, direct tumor microinjection)

Daratumumab BIOLOGICAL

Given intralesionally

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Treatment (FDG-PET, direct tumor microinjection)

Fludeoxyglucose F-18 DRUG

Undergo FDG-PET

Also known as: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Treatment (FDG-PET, direct tumor microinjection)

Gemcitabine Hydrochloride DRUG

Given intralesionally

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Treatment (FDG-PET, direct tumor microinjection)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (FDG-PET, direct tumor microinjection)

Nivolumab BIOLOGICAL

Given intralesionally

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (FDG-PET, direct tumor microinjection)

Obinutuzumab BIOLOGICAL

Given intralesionally

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (FDG-PET, direct tumor microinjection)

Pembrolizumab BIOLOGICAL

Given intralesionally

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (FDG-PET, direct tumor microinjection)

Positron Emission Tomography PROCEDURE

Undergo FDG-PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Treatment (FDG-PET, direct tumor microinjection)

Rituximab BIOLOGICAL

Given intralesionally

Also known as: 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

Treatment (FDG-PET, direct tumor microinjection)

Romidepsin DRUG

Given intralesionally

Also known as: 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

Treatment (FDG-PET, direct tumor microinjection)

Saline OTHER

Given intralesionally

Also known as: ISOTONIC SODIUM CHLORIDE SOLUTION, Sodium Chloride 0.9%

Treatment (FDG-PET, direct tumor microinjection)

Trastuzumab BIOLOGICAL

Given intralesionally

Also known as: 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

Treatment (FDG-PET, direct tumor microinjection)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Hodgkin Disease; Mycosis Fungoides; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Cutaneous; Lymphoma, B-Cell, Marginal Zone

Interventions

belinostat; carfilzomib; copanlisib; daratumumab; Fluorodeoxyglucose F18; Gemcitabine; Nivolumab; obinutuzumab; pembrolizumab; Magnetic Resonance Spectroscopy; Rituximab; CT-P10; romidepsin; Depsipeptides; Lactones; Sodium Chloride; Trastuzumab; PF-05280014; Ogivri; Ontruzant; trastuzumab biosimilar HLX02

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Antibodies, Monoclonal, Murine-Derived; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Grzegorz S. Nowakowski, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2018
• First Posted: February 14, 2018
• Study Start: March 27, 2018
• Primary Completion: August 26, 2022
• Study Completion: October 3, 2022
• Last Updated: May 26, 2025

Record last verified: 2025-05

Locations

US (1)