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

NCT03955640 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 19P.117JT 13333
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Metastatic Malignant Neoplasm in the Chest Wall; Recurrent Breast Carcinoma

Outcome Measures

Primary Outcomes (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).

  Up to 1 year post treatment

Secondary Outcomes (5)

• Local progression free-survival (PFS)

  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

• PFS

  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

• Best local overall response rate (ORR)

  Up to 1 year post treatment

• Quality of life (QOL)

  Up to 1 year post treatment

• Pain scores

  Up to 1 year post treatment

Other Outcomes (3)

• BRCA1/2 expression patterns

  Up to 1 year post treatment

• Homologous recombination (HR) capacity

  Up to 1 year post treatment

• Deoxyribonucleic acid (DNA) damage

  Up to 1 year post treatment

Study Arms (1)

Treatment (olaparib, hyperthermia)

EXPERIMENTAL

Patients 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.

Drug: Olaparib; Procedure: Hyperthermia Treatment; Other: Questionnaire Administration; Other: Quality-of-Life Assessment

Interventions

Olaparib DRUG

Given PO

Also known as: 763113-22-0, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Treatment (olaparib, hyperthermia)

Hyperthermia Treatment PROCEDURE

Undergo hyperthermia treatment

Also known as: Clinical Hyperthermia, Diathermy, Hyperthermia, hyperthermia therapy

Treatment (olaparib, hyperthermia)

Questionnaire Administration OTHER

Ancillary studies

Treatment (olaparib, hyperthermia)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (olaparib, hyperthermia)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AstraZeneca: collaborator
• Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

olaparib; Diathermy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Hyperthermia, Induced; Therapeutics

Study Officials

• Maysa Abu-Khalaf, MD

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  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: May 16, 2019
• First Posted: May 20, 2019
• Study Start: May 20, 2019
• Primary Completion: August 26, 2021
• Study Completion: August 26, 2021
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

US (1)