Olaparib and Durvalumab in Treating Participants With Metastatic Triple Negative Breast Cancer

NCT03544125 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00018239NCI-2018-00819
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I trial studies whether it is feasible to conduct a detailed molecular profile of triple negative breast cancer as part of a treatment strategy that asks whether or not we can lower the chance of breast cancer growing or spreading, by treating with a combination of PARP inhibitor how well (olaparib) and immune therapy (durvalumab). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and durvalumab may work better in treating participants with metastatic triple negative breast cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Prognostic Stage IV Breast Cancer AJCC v8; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of completion of Clinical Laboratory Improvement Act (CLIA) analytics on pre-treatment biopsy before the planned for 4-week biopsy

  Using the feasibility analysis set, the proportion of the completed CLIA analytics within 4 weeks (i.e., from day 1, cycle 1 up to day 1 cycle 2 of on-study treatment regimen will be estimated relative to all screened participants who undergo a first biopsy with a 95% confidence interval.

  At day 28

Secondary Outcomes (6)

• Incidence of >= grade 3 adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03

  Up to 3 months post treatment

• Overall response rate (ORR) for olaparib in combination with durvalumab

  Up to 6 months post treatment

• Clinical benefit rate (CBR) for olaparib in combination with durvalumab

  At 6 months post treatment

• Duration of response (DOR) for olaparib in combination with durvalumab

  Up to 6 months

• Progression-free survival (PFS) for olaparib in combination with durvalumab

  Up to 1-year post treatment

Study Arms (1)

Treatment (olaparib, durvalumab)

EXPERIMENTAL

Participants receive olaparib PO twice a day BID for 28 days in the absence of disease progression or unacceptable toxicity. Participants then receive olaparib PO BID on days 1-28 and durvalumab IV over 1 hour on day 1. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Participants may continue on therapy beyond disease progression at the discretion of the investigator.

Biological: Durvalumab; Drug: Olaparib

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (olaparib, durvalumab)

Olaparib DRUG

Given PO

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

Treatment (olaparib, durvalumab)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document.
• Metastatic triple negative breast cancer (TNBC), as defined by:
• Estrogen receptor (ER) and progesterone receptor (PR) negative as defined as ER \< 10% and PR \< 10% by immunohistochemistry according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing
• Human epidermal growth factor receptor 2 (HER2) non-amplified per ASCO/CAP guidelines, defined as:
• immunohistochemistry (IHC) score 0/1+
• IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to CEP17 \< 2.0, and if reported, average HER2 gene copy number \< 4 signals/cells; or
• ISH non-amplified with a ratio of HER2 to chromosome enumeration probe 17 (CEP17) \< 2.0, and if reported, average HER2 gene copy number \< 4 signals/cells
• Participants must have at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 that is amendable to biopsy.
• Prior therapies for metastatic breast cancer
• Frontline patients who have not received prior systemic therapy for metastatic breast cancer are eligible,
• Patients who have received =\< 2 prior chemotherapy regimens for metastatic breast cancer are eligible
• Participants must have fully recovered from the acute toxic effects of all prior treatment to grade 1 or less, except alopecia and =\< grade 2 neuropathy which are allowed
• Participants' life expectancy must be \> 6 months
• Participant must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Participant must consent to undergo a pre-treatment screening biopsy for enrollment and subsequent biomarker analyses.

You may not qualify if:

• Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent of device.
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure (New York Heart Association grade \>= 2) uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment
• Fridericia's correction formula (QTcF) \> 470 msec for females, or \> 450 msec for males, on screening electrocardiography (ECG) or congenital long QT syndrome
• Acute myocardial infarction or unstable angina pectoris \< 6 months prior to screening
• Note: Local surgery of isolated lesions for palliative intent is acceptable per investigator discretion.
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Participants with vitiligo or alopecia
• Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Participants without active disease in the last 5 years may be included but only after consultation with the study physician
• Participants with celiac disease controlled by diet alone

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator
• Prospect Creek Foundation: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Sun C, Fang Y, Labrie M, Li X, Mills GB. Systems approach to rational combination therapy: PARP inhibitors. Biochem Soc Trans. 2020 Jun 30;48(3):1101-1108. doi: 10.1042/BST20191092.

  PMID: 32379297 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

durvalumab; Immunoglobulin G; Disulfides; olaparib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Zahi Mitri, MD, MS

  OHSU Knight Cancer Institute

  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: Principal Investigator

Study Record Dates

• First Submitted: May 21, 2018
• First Posted: June 1, 2018
• Study Start: May 3, 2018
• Primary Completion: August 7, 2018
• Study Completion: November 18, 2020
• Last Updated: November 20, 2020

Record last verified: 2020-11

Locations

US (1)