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Metastatic Breast CancerPhase 2NCT03608865

Durvalumab (MEDI4736) and Tremelimumab in Hormone Receptor-positive, Hypermutated Metastatic Breast Cancer Identified by Whole Exome Sequencing

A Phase 2 study testing Durvalumab with Tremelimumab in people with Metastatic Breast Cancer, run by Yonsei University at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Abbreviated Title : Durvalumab + tremelimumab in hypermutated breast cancer Trial Phase : II Clinical Indication : Hormone receptor-positive metastatic breast cancer Trial Type : Interventional Type of control : None Route of administration : Intravenous Trial Blinding : None Treatment Groups : Durvalumab +… Read more about this study

Who is it for?
Ages 19 years and older, women only
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Durvalumab with Tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteSouth Korea
Study dates
19 Sep 2017to 24 Nov 2021
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 19 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  • Pre or postmenopausal women with stage IV hormone receptor-positive breast cancer by histological or cytological confirmation
  • Age > 19 years at time of study entry
  • Progression after one line of any systemic therapy (endocrine, targeted or chemotherapy) in the metastatic setting
  • 2.1 or more nonsynonymous mutations per megabase (Mb) by WES
  • Subject who has biopsy-accessible tumor
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  • At least one measurable lesion by RECIST 1.1. Biopsied tumor may be counted a measurable lesion if it is not excised
  • Documented disease progression on the most recent therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 ~ 1
  • Life expectancy of > 12 weeks
  • Adequate normal organ and marrow function as defined below:
  • Haemoglobin ≥ 9.0 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). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
  • Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: ① Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL), ② Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
  • 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. Otherwise, subjects must adhere to acceptable forms of birth control (a physician-approved contraceptive method: oral, injectable, or implantable hormonal contraceptive; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner).
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Who cannot join

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study
  • Participation in another clinical study with an investigational product during the last 4 weeks
  • Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab
  • Previous or coexisting malignancies. However, malignancies that have been curatively treated >5 years prior to study entry can be included. Exceptionally, cervical cancer in-situ, basal cell carcinoma, papillary thyroid carcinoma and superficial bladder tumors (T1a and Tis) can be included anytime after curative treatment
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug and within 6 weeks for nitrosourea or mitomycin C) for sufficient wash-out time
  • Palliative radiation, whole brain radiotherapy (WBRT), or gamma knife surgery (GKS) for brain metastases ≤ 2 weeks prior to initiation of study medication. Major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to initiation of study medication. Majority or minority of surgery can be decided at the investigator's discretion. Subjects who received these local therapy may be enrolled after predetermined time period
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  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
  • Any unresolved toxicity (≥CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
  • Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • History of primary immunodeficiency
  • History of allogeneic organ transplant
  • History of hypersensitivity to durvalumab or tremelimumab
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis A (anti-HAV antibody+), hepatitis B (HBs antigen+), hepatitis C (anti-HCV antibody+) or human immunodeficiency virus (HIV-1 or HIV-2 antibody+ or HTLV-1 antibody+), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  • Known history of previous clinical diagnosis of tuberculosis
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Symptomatic brain metastasis or leptomeningeal seeding. However, after WBRT or GKS for symptomatic brain or leptomeningeal metastases, if subjects are stable for 4 weeks without steroid and the dosage of anti-convulsant is stable for 4 weeks, they are eligible. Asymptomatic central nervous system metastases are eligible if the subject has no abnormal findings on neurologic examination and is not receiving corticosteroid therapy to control symptoms
  • Subjects with uncontrolled seizures
  • Female patients who are pregnant or breastfeeding or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Yonsei Cancer Center, Severance Hospital, Yonsei University Health System

    Seoul, 03722

Other trials in South Korea

About this study

Official title: Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab in Hormone Receptor-positive, Hypermutated Metastatic Breast Cancer Identified by Whole Exome Sequencing

Abbreviated Title : Durvalumab + tremelimumab in hypermutated breast cancer Trial Phase : II Clinical Indication : Hormone receptor-positive metastatic breast cancer Trial Type : Interventional Type of control : None Route of administration : Intravenous Trial Blinding : None Treatment Groups : Durvalumab + tremelimumab Number of trial subjects : Approximately 150 patients will be prescreened with whole exome sequencing. Then 30 patients will be enrolled in the treatment phase.

Estimated enrollment period : 24 months Estimated duration of trial : The sponsor estimates that the trial will require approximately 48 months from the time the first subject signs the informed consent until the last subject's last visit.

Duration of Participation : 24 months Estimated average length of treatment per patient : 8 months

Being tested
Durvalumab with Tremelimumab
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Durvalumab with TremelimumabDrug

    Trial treatment should be administered on Day 1 of each cycle after all procedures/assessments have been completed as detailed on the Trial Flow Chart. Trial treatment may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons. All trial treatments will be administered on an outpatient basis. Durvalumab 1500mg + tremelimumab 750 mg will be administered as a 60 minute each one IV infusion every 4 weeks. Sites should make every effort to target infusion timing to be as close to 60 minutes as possible. However, given the variability of infusion pumps from site to site.

Study groups in NCT03608865
Study groupRoleWhat they receive
experimental groupExperimentalDrug:Durvalumab + tremelimumab Dose/Potency:Durvalumab 1500mg(up to 4cycle) / tremelimumab 75mg(up to 13 cycle) Dose Frequency:Q4W Route of Administration:IV infusion Regimen/Treatment Period:Day 1 of each 4 week cycle Use:Experimental
Receives: Drug: Durvalumab with Tremelimumab

What is being measured

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

  1. Objective response rate (ORR) by RECIST 1.1

    To evaluate objective response rate (ORR) based on RECIST 1.1 in hormone receptor-positive, hypermutated metastatic breast cancer identified by whole exome sequencing (WES) Hypothesis: Durvalumab + tremelimumab in patients with hormone receptor-positive, hypermutated metastatic breast cancer identified by WES will result in clinically meaningful ORR based on RECIST 1.1

    Measured: up to 4 years (the end of study)

Secondary outcomes (4)

  1. Clinical benefit rate (CBR) by RECIST 1.1 defined by complete or partial response or stable disease for at least 24 weeks

    To evaluate clinical benefit rate (CBR) by RECIST 1.1 defined by complete or partial response or stable disease for at least 24 weeks

    Measured: every 1 year up to 4 years (the end of study)

  2. Duration of response (DoR)

    To evaluate duration of response (DoR)

    Measured: every 1 year up to 4 years (the end of study)

  3. Disease control rate (DCR) by RECIST 1.1

    To evaluate disease control rate (DCR) by RECIST 1.1

    Measured: every 1 year up to 4 years (the end of study)

  4. Progression-free survival (PFS) by RECIST 1.1

    To evaluate progression-free survival (PFS) by RECIST 1.1

    Measured: every 1 year up to 4 years (the end of study)

Timeline

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

  1. First posted1 Aug 2018
  2. Study start19 Sep 2017
  3. Primary completion24 Nov 2021
  4. Study completion24 Nov 2021

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Drug:Durvalumab + tremelimumab Dose/Potency: Durvalumab 1500mg(up to 4cycle) / tremelimumab 75mg(up to 13 cycle) Dose Frequency:Q4W Route of Administration:IV infusion Regimen/Treatment Period:Day 1 of each 4 week cycle Use:Experimental
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03608865
Sponsor's protocol ID
4-2016-0912
Status last verified
Dec 2021
First submitted
23 Jul 2018
Last updated
3 Jan 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab with Tremelimumab in people with Metastatic Breast Cancer, run by Yonsei University at 1 site in South Korea.

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 19 inclusion and 22 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: finished, as of the sponsor's last update on 3 Jan 2022. 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 South Korea. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Objective response rate (ORR) by RECIST 1.1 (time frame: up to 4 years (the end of study)). 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 NCT03608865.

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 3 Jan 2022.

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