Breast CancerPhase 2EURO-DIGNITYNCT02850419
Heat-Activated Target Therapy of Local-Regional Relapse in Breast Cancer Patients
A Phase 2 study testing ThermoDox (Thermally Sensitive Liposomal Doxorubicin), Radiation Therapy and Superficial Hyperthermia in people with Breast Cancer, run by Imunon at 3 sites in 3 countries.
Trial summary
The 105-15-201 study is designed to assess the effectiveness and tolerability of the combination of heat-activated target therapy (radiotherapy + hyperthermia + lyso-thermosensitive liposomal doxorubicin) of loco-regional relapse in breast cancer patients. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- ThermoDox (Thermally Sensitive Liposomal Doxorubicin), Radiation Therapy and Superficial Hyperthermia
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Mar 2017to Feb 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically documented recurrent adenocarcinoma of the breast with a recurrence on the chest wall or its overlying skin:
- Ulcerative chest wall disease defined as non-healing wounds consistent with cancer.
- Inflammatory breast carcinoma.
- Breast carcinoma not resected for medical reasons.
- Tumor thickness, must be clinically indicated for hyperthermia therapy, as measured by clinical exam or radiological imaging studies (CT or MRI). The target local tumor lesion(s) must be able to be covered within two hyperthermia fields of treatment.
- LRR Disease progression despite other available standard treatment options based on what is clinically indicated according to the investigator's clinical and medical judgment, including: one or more radiation treatment(s) to the chest wall
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- Patients with stable distant bone metastasis; concomitant treatment with Zoledronic acid and Denosumab is allowed
- Non-pregnant female at least 18 years of age. If subject is of child-bearing age, must have a negative serum pregnancy test at baseline and must agree to practice an acceptable form of birth control while on the study.
- Provide written informed consent and willing to comply with the protocol requirements.
Who cannot join
- No concomitant cytotoxic antineoplastic therapy is allowed. Prior chemotherapy should not be administered within 5 half-lives or 28 days whichever is shorter.
- Prior confirmed allergic reaction (including moderate rash, dyspnea, wheezing, urticaria or other symptoms) attributed to the administration of either anthracyclines or other liposomally encapsulated drugs that required discontinuation of prior therapy.
- Patients who have previously received hyperthermia in conjunction with either radiation therapy or chemotherapy.
- Previous treatment with anthracyclines exceeding the following dosages: free doxorubicin (i.e. non- liposomal) and/or liposomal doxorubicin ≥300 mg/m2 epirubicin free > 540 mg / m2.
- Previous (required active treatment within 5 years) or concomitant malignancy except basal cell cancer, in situ carcinoma of the cervix, or contralateral breast cancer. Subjects with a prior contralateral breast malignancy can be included if they did not receive any chemotherapy.
- Baseline laboratories (to establish eligibility): · Granulocytes ......< 1,500/ microliter · Platelets .......... < 75,000/ microliter · Hemoglobin ... < 9 gm/dL Total Bilirubin ... > 2 mg/dL ALT and AST ...> 2.5X upper limit of normal Creatinine ......... > 1.5 X upper limit of normal.
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- ECOG/Zubrod Performance Status > 2.
- MUGA/Echocardiogram Left Ventricular Ejection Fraction < 50%.
- History of: acute coronary syndrome, cerebral vascular accident, abnormal cardiac stress testing within last 6 months, symptomatic coronary artery disease, uncontrolled hypertension or cardiomyopathy and cardiac valvular surgery or open heart surgery.
- Conditions which may interfere with hyperthermia portion of the trial such as: functioning cardiac pacemaker; metal plates, rods or prosthesis of the chest wall, breast reconstruction with implants, severe numbness and/or tingling of the chest wall or breast, skin grafts and/or flaps on the breast/CW.
- Serious active infection requiring long-term antibiotic treatment.
- Has received any external radiation therapy within 60 days prior to study enrollment.
- Patients with parenchymal and known brain metastases; if metastasis is operated or irradiated the patient can be included in the study.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: Heat-Activated Target Therapy (Radiotherapy + Hyperthermia + Lyso-Thermosensitive Liposomal Doxorubicin) of Local-Regional Relapse in Breast Cancer Patients
The 105-15-201 study is designed to assess the effectiveness and tolerability of the combination of heat-activated target therapy (radiotherapy + hyperthermia + lyso-thermosensitive liposomal doxorubicin) of loco-regional relapse in breast cancer patients.
Read the detailed description
Locoregional recurrence of breast cancer (LRR) after mastectomy is a clinically challenging problem. Between 5% and 35% of women with operable breast cancer will experience an isolated LRR following their primary treatment, usually within 5 years of initial mastectomy. LRR or LR typically causes pain, lymphedema, and/or loss of freedom of movement. Therapeutic options usually involve resection, radiation or, at some specialized centers, combined radiation and hyperthermia. However, local control remains suboptimal in previously irradiated chest wall patients with the combination of radiation and hyperthermia providing local control rates of about 65%.
Lyso-thermosensitive liposomal doxorubicin (LTLD) is a temperature sensitive liposome which is systemically administered and is engineered to selectively release its doxorubicin contents when exposed to temperatures ≥ 39.5°C.
Local mild hyperthermia (40 to 44°C) is cytotoxic and is known to have an immunomodulatory effect along with a radiation and chemosensitizing effect in the heated tissue. Furthermore, mild hyperthermia enhances leakiness of tumor tissue, increases local perfusion and upregulates transvascular transport of doxorubicin.
Radiation therapy will be administered in this combination therapy.
This study evaluates the application of a tri-modal approach with LTLD to improve outcome: radiation, hyperthermia, and targeted release of a novel formulation of doxorubicin.
- Conditions
- Breast Cancer
- Being tested
- ThermoDox (Thermally Sensitive Liposomal Doxorubicin), Radiation Therapy, Superficial Hyperthermia
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThermoDox (Thermally Sensitive Liposomal Doxorubicin)Drug
A dose of 40 mg/m2 will be administered at each cycle for a total of 6 cycles. ThermoDox will be administered in conjunction with hyperthermia.
Radiation TherapyRadiation
A total of 40 Gy in 20 fractions of 2 Gy per fraction will be administered. Up to 66 Gy of radiation therapy can be administered however institutional guidelines should be followed.
Superficial HyperthermiaDevice
Thermal dose is an one-hour treatment at a temperature between 40 and 43 degrees Celsius at the target site.
| Study group | Role | What they receive |
|---|---|---|
| ThermoDox (40mg/m2)+hyperthermia+RT | Experimental | Treatment will consist of up to six cycles of LTLD combined with hyperthermia every 21 days with the first day of each cycle being Day 1. ThermoDox will be administered at a dose of 40 mg/m2. Thermal dose is a one-hour treatment at a temperature between 40 and 43°C at the target site. At Cycle 1, radiotherapy will begin and will be combined with hyperthermia. A total of 40 Gy in 20 fractions of 2 Gy per fraction will be administered. Up to 66 Gy of radiation therapy can be administered however institutional guidelines should be followed. Receives: Drug: ThermoDox (Thermally Sensitive Liposomal Doxorubicin); Radiation: Radiation Therapy; Device: Superficial Hyperthermia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: Up to 12 months
Loco-regional breast tumor control in patient who underwent ThermoDox + hyperthermia + radiotherapy as measured by target lesion clinical response rate combining RECIST criteria with digital photography to gauge response.
Measured: Up to 18 months
Secondary outcomes (3)
Duration of local control [CR (complete response), PR (partial response) and SD (stable disease) following treatment with ThermoDox + Hyperthermia + Radiotherapy up to 12 months among patients with LRR breast cancer.
Measured: Up to 18 months
Patient Reported Quality of Life using the FACT-B following treatment with ThermoDox + Hyperthermia + Radiotherapy among patients with LRR breast cancer.
Measured: Up to 18 months
Patient Reported Quality of Life using the Brief Pain Inventory (BPI) following treatment with ThermoDox + Hyperthermia + Radiotherapy among patients with LRR breast cancer.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2016 (estimated)
- Study startMar 2017 (estimated)
- Primary completionDec 2019 (estimated)
- Study completionFeb 2020 (estimated)
Why it stopped: Administrative
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imunon
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pietro Gabriele, M.D., Principal investigator, FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA - IRCCS CANDIOLO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02850419
- Sponsor's protocol ID
- 105-15-201
- Acronym
- EURO-DIGNITY
- Status last verified
- Mar 2022
- First submitted
- 26 Jul 2016
- Last updated
- 7 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heat-Activated Target Therapy (Radiotherapy + Hyperthermia + Lyso-Thermosensitive Liposomal Doxorubicin) of Local-Regional Relapse in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT02850419
- Acronym / sponsor ID
- EURO-DIGNITY / 105-15-201
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Administrative
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ImunonIndustry (pharma, biotech, devices)
- Study start
- Mar 2017 (estimated)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Feb 2020 (estimated)
- First posted
- 1 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The 105-15-201 study is designed to assess the effectiveness and tolerability of the combination of heat-activated target therapy (radiotherapy + hyperthermia + lyso-thermosensitive liposomal doxorubicin) of loco-regional relapse in breast cancer patients.
Detailed description
Locoregional recurrence of breast cancer (LRR) after mastectomy is a clinically challenging problem. Between 5% and 35% of women with operable breast cancer will experience an isolated LRR following their primary treatment, usually within 5 years of initial mastectomy. LRR or LR typically causes pain, lymphedema, and/or loss of freedom of movement. Therapeutic options usually involve resection, radiation or, at some specialized centers, combined radiation and hyperthermia. However, local control remains suboptimal in previously irradiated chest wall patients with the combination of radiation and hyperthermia providing local control rates of about 65%.
Lyso-thermosensitive liposomal doxorubicin (LTLD) is a temperature sensitive liposome which is systemically administered and is engineered to selectively release its doxorubicin contents when exposed to temperatures ≥ 39.5°C.
Local mild hyperthermia (40 to 44°C) is cytotoxic and is known to have an immunomodulatory effect along with a radiation and chemosensitizing effect in the heated tissue. Furthermore, mild hyperthermia enhances leakiness of tumor tissue, increases local perfusion and upregulates transvascular transport of doxorubicin.
Radiation therapy will be administered in this combination therapy.
This study evaluates the application of a tri-modal approach with LTLD to improve outcome: radiation, hyperthermia, and targeted release of a novel formulation of doxorubicin.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ThermoDox (40mg/m2)+hyperthermia+RT | Experimental | Drug: ThermoDox (Thermally Sensitive Liposomal Doxorubicin), Radiation: Radiation Therapy, Device: Superficial HyperthermiaTreatment will consist of up to six cycles of LTLD combined with hyperthermia every 21 days with the first day of each cycle being Day 1. ThermoDox will be administered at a dose of 40 mg/m2. Thermal dose is a one-hour treatment at a temperature between 40 and 43°C at the target site. At Cycle 1, radiotherapy will begin and will be combined with hyperthermia. A total of 40 Gy in 20 fractions of 2 Gy per fraction will be administered. Up to 66 Gy of radiation therapy can be administered however institutional guidelines should be followed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically documented recurrent adenocarcinoma of the breast with a recurrence on the chest wall or its overlying skin:
- Tumor thickness, must be clinically indicated for hyperthermia therapy, as measured by clinical exam or radiological imaging studies (CT or MRI). The target local tumor lesion(s) must be able to be covered within two hyperthermia fields of treatment.
- LRR Disease progression despite other available standard treatment options based on what is clinically indicated according to the investigator's clinical and medical judgment, including: one or more radiation treatment(s) to the chest wall
- Patients with stable distant bone metastasis; concomitant treatment with Zoledronic acid and Denosumab is allowed
- Non-pregnant female at least 18 years of age. If subject is of child-bearing age, must have a negative serum pregnancy test at baseline and must agree to practice an acceptable form of birth control while on the study.
Key exclusion criteria (13 listed)
- No concomitant cytotoxic antineoplastic therapy is allowed. Prior chemotherapy should not be administered within 5 half-lives or 28 days whichever is shorter.
- Prior confirmed allergic reaction (including moderate rash, dyspnea, wheezing, urticaria or other symptoms) attributed to the administration of either anthracyclines or other liposomally encapsulated drugs that required discontinuation of prior therapy.
- Patients who have previously received hyperthermia in conjunction with either radiation therapy or chemotherapy.
- Previous treatment with anthracyclines exceeding the following dosages: free doxorubicin (i.e. non- liposomal) and/or liposomal doxorubicin ≥300 mg/m2 epirubicin free > 540 mg / m2.
- Previous (required active treatment within 5 years) or concomitant malignancy except basal cell cancer, in situ carcinoma of the cervix, or contralateral breast cancer. Subjects with a prior contralateral breast malignancy can be included if they did not receive any chemotherapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ThermoDox (Thermally Sensitive Liposomal Doxorubicin)A dose of 40 mg/m2 will be administered at each cycle for a total of 6 cycles. ThermoDox will be administered in conjunction with hyperthermia. | Drug | ThermoDox (40mg/m2)+hyperthermia+RT |
| Radiation TherapyA total of 40 Gy in 20 fractions of 2 Gy per fraction will be administered. Up to 66 Gy of radiation therapy can be administered however institutional guidelines should be followed. | Radiation | ThermoDox (40mg/m2)+hyperthermia+RT |
| Superficial HyperthermiaThermal dose is an one-hour treatment at a temperature between 40 and 43 degrees Celsius at the target site. | Device | ThermoDox (40mg/m2)+hyperthermia+RT |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Up to 12 months
Loco-regional breast tumor control in patient who underwent ThermoDox + hyperthermia + radiotherapy as measured by target lesion clinical response rate combining RECIST criteria with digital photography to gauge response.
Time frame: Up to 18 months
3 secondary outcomes
Duration of local control [CR (complete response), PR (partial response) and SD (stable disease) following treatment with ThermoDox + Hyperthermia + Radiotherapy up to 12 months among patients with LRR breast cancer.
Time frame: Up to 18 months
Patient Reported Quality of Life using the FACT-B following treatment with ThermoDox + Hyperthermia + Radiotherapy among patients with LRR breast cancer.
Time frame: Up to 18 months
Patient Reported Quality of Life using the Brief Pain Inventory (BPI) following treatment with ThermoDox + Hyperthermia + Radiotherapy among patients with LRR breast cancer.
Time frame: Up to 18 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pietro Gabriele, M.D. principal investigator
FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA - IRCCS CANDIOLO
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ThermoDox (Thermally Sensitive Liposomal Doxorubicin), Radiation Therapy and Superficial Hyperthermia in people with Breast Cancer, run by Imunon at 3 sites in 3 countries.
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 9 inclusion and 13 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: withdrawn, as of the sponsor's last update on 7 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Czechia, Israel, Italy. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: Up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Apr 2022.