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Metastatic Malignant Neoplasm in the Chest WallPhase 1NCT03955640

Hyperthermia and Olaparib in Treating Breast Cancer Patients With Chest Wall Recurrences

A Phase 1 study testing Olaparib, Hyperthermia Treatment and Questionnaire Administration in people with Metastatic Malignant Neoplasm in the Chest Wall and Recurrent Breast Carcinoma, run by Thomas Jefferson University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of olaparib when given with hyperthermia in treating patients with breast cancer that has come back in the chest wall. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 to 80 years, women only
What is being tested?
Olaparib, Hyperthermia Treatment and Questionnaire Administration
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
20 May 2019to 26 Aug 2021
Phase
Phase 1
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 to 80 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients regardless of estrogen receptor (ER)/progesterone receptor (PR)/HER2 status and have breast cancer recurrence on the chest wall
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
  • Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses
  • Hemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days prior to administration of study treatment)
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (measured within 28 days prior administration of study treatment)
  • Platelet count >= 100 x 10^9/L (measured within 28 days prior to administration of study treatment)
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  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =< 5x ULN (measured within 28 days prior to administration of study treatment)
  • Patients must have creatinine clearance estimated of >= 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test (measured within 28 days prior to administration of study treatment)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must have a life expectancy >= 16 weeks
  • Breast cancer with chest wall disease that is at least 2 cm in size at the greatest dimension
  • Patients will be eligible for this trial regardless of number of lines of therapy and after adjuvant chemotherapy with recurrence on the chest wall
  • Patients with hormone receptor positive disease who discontinue endocrine therapy two weeks prior to initiating study treatment are eligible
  • Body mass index (BMI): 15 to 50 at the time of consent
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of initiating study treatment and confirmed prior to treatment on day 1 and willingness to use effective contraception during study treatment and for at least 30 days after last dose of study drug. Postmenopausal is defined as:
  • Amenorrhea for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
  • Radiation-induced oophorectomy with last menses > 1 year ago
  • Chemotherapy-induced menopause with > 1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)

Who cannot join

  • As judged by the investigator, any evidence of non-compliance which in the investigator's opinion makes it undesirable for the patient to participate in the trial
  • Patients with rapidly progressing disease
  • Metastatic disease should not be progressing so as to require systemic treatment within 4 weeks of enrollment based on clinical assessment by the investigator
  • Metastatic disease should not be progressing so as to require palliative treatment within 4 weeks of enrollment based on clinical assessment by the investigator
  • Other malignancy unless curatively treated with no evidence of disease for >= 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma
  • Resting electrocardiogram (EKG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fridericia [QTcF] prolongation > 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
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  • Persistent toxicities caused by previous cancer therapy >= grade 2, excluding alopecia and neuropathy
  • Patients with current or previous diagnosis of myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
  • Patients with symptomatic uncontrolled brain metastases or spinal cord metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
  • Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
  • Any previous treatment with PARP inhibitor, including olaparib
  • Subjects with a known hypersensitivity to olaparib or any of the excipients of the product
  • Patients with a known hypersensitivity to hyperthermia
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
  • Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks
  • Concomitant use of known strong CYP3A inducers (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of surgery
  • Patients with known active hepatitis B or C
  • Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable outside of 28 days prior to enrollment)
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
  • Any patient with a known germline BRCA1 or 2 mutation
  • Participation in another clinical study with an investigational product administered in the last 2 months
  • Previous enrollment in the present study
  • Breast feeding women
  • Involvement in the planning and/or conduct of the study
  • No radiotherapy, treatment with cytotoxic agents, biologic agents within 3 weeks prior to beginning treatment on this study. Patients must have recovered from the acute toxicities of any prior treatment with cytotoxic drugs to =< grade 1 (allowance for grade 2 alopecia and neuropathy) in order to be eligible. Patients who underwent post-mastectomy radiation will not be excluded from this study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Pilot Trial of Hyperthermia in Combination With Olaparib in Breast Cancer Patients With Chest Wall Recurrences

This phase I trial studies the side effects and best dose of olaparib when given with hyperthermia in treating patients with breast cancer that has come back in the chest wall. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hyperthermia treatment may kill or damage tumor cells by heating them to several degrees above normal body temperature. Giving olaparib and hyperthermia treatment may work better in treating patients with breast cancer that has come back in the chest well compared to standard of care.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the dose limiting toxicities and maximum tolerated dose of olaparib given in combination with chest wall hyperthermia in patients with locally advanced or metastatic breast cancer with chest wall recurrences who have wild-type BRCA status (patients with germline BRCA mutations are excluded from this study).

SECONDARY OBJECTIVES:

  1. To determine the local progression free survival (in months) for patients with chest wall recurrences defined as time to progression of disease on chest wall with olaparib with hyperthermia.

II. To determine the 1-year progression free survival (in months) for patients with chest wall recurrences treated with olaparib with hyperthermia.

III. To determine the best local overall response rate of chest wall after the combination of hyperthermia and olaparib.

IV. To determine the quality of life and pain scores before, during and after treatment as measured by the Edmonton Symptom Assessment System which includes a pain score and 8 other subjective measures of wellness for cancer patients (0 to 10).

EXPLORATORY OBJECTIVES:

  1. To evaluate BRCA1/2 levels by immunohistochemistry and explore if hyperthermia induced BRCA1/2 expression.

II. To evaluate HR (homologous recombination) competency by RAD51 foci and explore if hyperthermia induces homologous recombination in breast tissue.

III. To explore deoxyribonucleic acid (DNA) damage as measured by gammaH2AX and comet assay in cells dissociated from biopsy tissues.

OUTLINE: This is a dose-escalation study of olaparib.

Patients receive olaparib orally (PO) twice daily (BID). Treatment continues for 4 weeks in the absence of disease progression and unacceptable toxicity. Beginning week 2, patients also undergo hyperthermia treatment over 1 hour twice weekly for 3 weeks in the absence of disease progression and unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 12 months.

Being tested
Olaparib, Hyperthermia Treatment, Questionnaire Administration, Quality-of-Life Assessment
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlaparibDrug

    Also called 763113-22-0, AZD2281, KU-0059436, Lynparza

    Given PO

  • Hyperthermia TreatmentProcedure or surgery

    Also called Clinical Hyperthermia, Diathermy, Hyperthermia, hyperthermia therapy

    Undergo hyperthermia treatment

  • Questionnaire AdministrationOther

    Ancillary studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT03955640
Study groupRoleWhat they receive
Treatment (olaparib, hyperthermia)ExperimentalPatients receive olaparib PO BID. Treatment continues for 4 weeks in the absence of disease progression and unacceptable toxicity. Beginning week 2, patients also undergo hyperthermia treatment over 1 hour twice weekly for 3 weeks in the absence of disease progression and unacceptable toxicity.
Receives: Drug: Olaparib; Procedure: Hyperthermia Treatment; Other: Questionnaire Administration; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Will be continually assessed according to the National Cancer Institute Common Toxicity Criteria for Adverse Advents (CTCAE version [v]5.0).

    Measured: Up to 1 year post treatment

Secondary outcomes (5)

  1. Local progression free-survival (PFS)

    Will be reported as Kaplan-Meier survival curves with the median survival time with 95% confidence interval. Will be analyzed using log-rank test as well as Cox proportional hazard models.

    Measured: From first dose of olaparib to the date of the first documented disease progression or recurrence on the chest wall, assessed up to 1 year

  2. PFS

    Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Will be reported as Kaplan-Meier survival curves with the median survival time with 95% confidence interval. Will be analyzed using log-rank test as well as Cox proportional hazard models.

    Measured: From first dose of olaparib to the date of the first documented disease progression or recurrence, or death due to any cause, whichever occurs first, assessed up to 1 year

  3. Best local overall response rate (ORR)

    Defined as the number of subjects with a best overall response (BOR) defined as a complete response (CR) or partial response (PR) divided by the number of enrolled subjects. The proportion of patients will be summarized together with the appropriate 95% confidence interval. The binary endpoint of ORR will be compared by test on proportions.

    Measured: Up to 1 year post treatment

  4. Quality of life (QOL)

    Defined by the Edmonton Symptom Assessment System (ESAS) using nine subjective patient measures of well-being including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath. These will be rated by the patients during each visit (visits 1-6) and the change in values will correlate to an improvement in quality of life (a positive change will correlate to an improvement and a negative change will correlate to a worsening of pain). The multinominal/ordinal endpoints in QOLs will be summarized in frequencies ad proportions and compared using trend test.

    Measured: Up to 1 year post treatment

  5. Pain scores

    Defined by the Edmonton Symptom Assessment System (ESAS) using nine subjective patient measures of well-being including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath. These will be rated by the patients during each visit (visits 1-6) and the change in values will correlate to an improvement in quality of life (a positive change will correlate to an improvement and a negative change will correlate to a worsening of pain).

    Measured: Up to 1 year post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2019
  2. Study start20 May 2019
  3. Primary completion26 Aug 2021
  4. Study completion26 Aug 2021

Why it stopped: PI decided not to move forward because of low accrual

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03955640
Sponsor's protocol ID
19P.117
Other IDs
JT 13333
Status last verified
Dec 2025
First submitted
16 May 2019
Last updated
22 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Olaparib, Hyperthermia Treatment and Questionnaire Administration in people with Metastatic Malignant Neoplasm in the Chest Wall and Recurrent Breast Carcinoma, run by Thomas Jefferson University at 1 site in United States.

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 21 inclusion and 28 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: stopped early, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 stopped early (reason given: PI decided not to move forward because of low accrual). Results are not available in the source record.

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?

Incidence of adverse events (time frame: Up to 1 year post treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03955640.

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 22 Dec 2025.

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