Window of Opportunity Trial of Neoadjuvant Olaparib and Durvalumab for Triple Negative or Low ER+ Breast Cancer

NCT03594396 | Active Not Recruiting Phase 1

• 1 other identifier: S1709-101-888
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Window of Opportunity Trial of Olaparib and Durvalumab (MEDI4736) before Standard Neoadjuvant Chemotherapy for Stage II/III Triple Negative or Low ER+ Breast Cancer

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• The changes of tumor biology

  The changes of tumor biology detected by serial biopsy of breast cancer before and after olaparib and durvalumab (exploratory serial biopsy study)

  28 days

Secondary Outcomes (4)

• pathological complete response

  7 months

• Response rate

  7 months

• Treatment-related adverse events as assessed by CTCAE v4.0

  7 months

• Adverse events of special interest and immune-mediated adverse events

  7 months

Study Arms (1)

MEDIOLA

EXPERIMENTAL

Prior to the start of study medication, tumor tissue and blood will be collected as baseline. Olaparib 300mg bid will be started after the collection of tumor and blood. Olaparib will be given on days 1-28 days without rest. Tumor tissue and blood will be collected on day 14 before administration of durvalumab, to see the change in biomarkers after 2 weeks of olaparib treatment. After the acquisition of tumor and blood, durvalumab will be given in a fixed one dose of 1.5 gram on day 15. On day 29, there will be a third acquisition of tumor and blood, to see the change in biomarkers after combination treatment of olaparib and durvalumab. Tumor response will also be evaluated according to RECIST criteria version 1.1 based on CT.

Drug: Olaparib; Drug: Durvalumab

Interventions

Olaparib DRUG

Olaparib 300mg bid will be given on days 1-28 days without rest.

Also known as: Lynparza

MEDIOLA

Durvalumab DRUG

A fixed dose of durvalumab 1500 mg is given via IV infusion on Day 15.

Also known as: IMFINZI, MEDI4736

MEDIOLA

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Nineteen years of age or older on the day of signing informed consent.
• Willing and able to provide written informed consent for voluntary participation in the trial.
• Has previously untreated, clinical stage II/III triple negative breast cancer (TNBC) or low estrogen receptor (ER) tumor where ER is expressed in ≤10% tumor cells) .
• Willing to provide biopsies from the primary tumor or lymph nodes at screening to the central laboratory and agrees to have a core needle biopsy or incisional or excisional tumor biopsy after 14 days and 28 days of olaparib treatment (before and after durvalumab treatment) if tumor biopsy is feasible as judged by the investigator.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for \>1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry and agree to use contraception if they or their partner are of reproductive potential.
• Has adequate organ function.
• Hemoglobin ≥ 10.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN unless due to Gilbert's syndrome
• INR/PT/APTT each ≤ 1.5 x ULN
• TSH within normal limits
• Serum creatinine \< 1.5 x ULN or serum creatinine CL \> 51 mL/min by the Cockcroft-Gault formula (Cockroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance

You may not qualify if:

• Underweighted populations - ≤30kg
• Has evidence of metastatic breast cancer, inflammatory breast cancer, or concurrent bilateral invasive breast cancer where ER is expressed in \>10% tumor cells.
• (Note) Patients with bilateral invasive breast cancers can be enrolled if both tumors are TNBCs, including low estrogen receptor (ER) tumor where ER is expressed in ≤10% tumor cells.
• Has another malignancy within the last 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and thyroid cancer that has undergone potentially curative surgery, or in situ cervical cancer.
• (Note) These patients should be consulted to the principal investigator for a case-by-case decision before enrollment.
• Has received prior chemotherapy, targeted therapy, radiation therapy, immunotherapy that targets immune checkpoints, co-stimulatory or co-inhibitory pathways for T cell receptors within the past 12 months.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
• Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
• Has received a live vaccine within 30 days of the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine up to 30 days after the last dose of IP.
• Has an active autoimmune disease or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]) that has required systemic treatment in past 2 years. The followings are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment.
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 3 years may be included but only after consultation with the principal investigator.
• Patients with celiac disease controlled by diet alone may be included but only after consultation with the principal investigator.

Sponsors & Collaborators

• Seoul National University Hospital: lead
• AstraZeneca: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

olaparib; durvalumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Seock-Ah Im

  Seoul National University Hospital

  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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: July 20, 2018
• Study Start: June 29, 2018
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 17, 2025

Record last verified: 2024-12

Locations

KR (1)