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Breast CancerPhase 2ULTIMATENCT02997995

Durvalumab and Endocrine Therapy in ER+/Her2- Breast Cancer After CD8+ Infiltration Effective Immune-Attractant Exposure

A Phase 2 study testing Immune-attractant, Durvalumab and Biopsy in people with Breast Cancer and Estrogen Receptor Positive Tumor, run by UNICANCER at 29 sites in 3 countries.

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

This is an open-label, multicentric, international, phase II trial testing aromatase inhibitors in combination with durvalumab in patients with CD8+ T cell infiltration (>10% CD8+ T cells in the tumor). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Immune-attractant, Durvalumab and Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
29 sitesin 3 countries
Study dates
15 Feb 2017to 28 Aug 2020
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 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years post-menopausal according to one of the following criteria:
  • Age >60 years
  • Or Bilateral ovariectomy
  • Or Age ≤60, with an uterus and presenting an amenorrhea of more than 12 months and FSH and estradiol in the postmenopausal range
  • Or Age ≤60, without an uterus and FSH and estradiol in the postmenopausal range
  • Histologically proven invasive breast cancer eligible to neoadjuvant endocrine therapy according to multidisciplinary tumor board.
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  • Note: Multicentric/multifocal tumors are allowed if all share the same characteristics
  • cT2-T4, any N; cT2 are eligible only if the clinical tumor size is >3 cm
  • Non metastatic, M0 (according to clinical staging)
  • Luminal A patients ER-positive by immunohistochemistry (IHC) according to the following criteria (local assessment): Grade I or II AND ER-positive (≥60%) AND Ki67 <20%
  • Her2-negative by IHC (score 0 or 1+) and/or fluorescent in situ hybridization (FISH)/chromogenic in situ hybridization (CISH) negative according to local assessment
  • CD8+ T Cell infiltration defined as >10% cells stained with anti-CD8 monoclonal antibody by IHC at the 3-week biopsy (applicable for inclusion in part 2 only)
  • Available tumor samples from baseline biopsy
  • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment
  • Adequate organ and marrow function as defined below:
  • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count ≥1.5 × 10⁹/L
  • Platelet count ≥100 × 10⁹/L
  • Serum bilirubin ≤1.5 × upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician
  • Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5 × ULN
  • Adequate renal function as determined by CKD-EPI formula (using actual body weight)
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
  • Written informed consent obtained prior to performing any protocol-related procedures, including screening evaluations

Who cannot join

  • Inflammatory breast cancer
  • No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines
  • Any concurrent chemotherapy, investigational product (IP), biologic therapy for cancer treatment
  • Previous Radiotherapy treatment to more than 30% of the bone marrow;
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose
  • History of allogenic organ transplantation
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  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis with the exception of diverticulosis, celiac 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 within the past 3 years prior to the start of treatment. The following 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 condition that, in the opinion of the Investigator, would interfere with the evaluation of investigational product or interpretation of patient safety or study results, including ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from investigational products, or compromise the ability of the patient to give written informed consent
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
  • History of active primary immunodeficiency
  • Known history of active tuberculosis
  • Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
  • Current or prior use of immunosuppressive medication within 14 days before the first dose. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
  • Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
  • Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.
  • Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP
  • Known allergy or hypersensitivity to any medicinal product used in the trial or any excipient

Trial locations and contacts

29 sites in 3 countries.

29 sites in 3 countries

France21 sites

  • Centre Hospitalier cote Basque

    Bayonne, 64109

  • Institut Bergonié

    Bordeaux, 33000

  • Centre François Baclesse

    Caen

  • Centre Hospitalier de Cahors

    Cahors, 46000

  • Centre Hôspitalier de Cholet

    Cholet, 49300

  • Centre George François Leclerc

    Dijon, 21000

  • Institut Daniel Hollard Groupe Hôspitalier

    Grenoble, 38028

  • Centre Oscar Lambret

    Lille, 59020

  • CHU Limoges

    Limoges, 87042

  • Centre Hospitalier Bretagne Sud

    Lorient, 56100

  • Centre Léon Bérard

    Lyon, 69008

  • Institut Paoli Calmettes

    Marseille, 13009

  • Institut Curie Site Paris

    Paris, 75005

  • Hôpital Saint Louis APHP

    Paris, 75010

  • Centre Hospitalier Perpignan

    Perpignan, 66000

  • Institut Jean Godinot

    Reims, 51726

  • Institut Curie Hôpital René Huguenin

    Saint-Cloud, 92210

  • Centre Paul Strauss

    Strasbourg, 67065

  • Institut Claudius Regaud

    Toulouse, 31059

  • CHU Bretonneau - Centre Henry Kaplan

    Tours, 37044

  • Gustave Roussy

    Villejuif, 94800

Other trials in France

Spain7 sites

  • ICO Badalona

    Badalona

  • Hospital Clinic Barcelona

    Barcelona

  • HU Vall Hebron

    Barcelona

  • HU Arnau de Vilanova

    Lleida

  • CIO Clara Campal

    Madrid

  • HU Ramon y Cajal

    Madrid

  • Hospital Clínico Universitario de Valencia

    Valencia

Other trials in Spain

Sweden1 site

  • Sahlgrenska University Hospital

    Gothenburg

Other trials in Sweden

About this study

Official title: A Phase II Trial Testing Durvalumab Combined With Endocrine Therapy in Patients With ER+/Her2- Breast Cancer Eligible for Neoadjuvant Endocrine Therapy And Who Present CD8+ T Cell Infiltration After 4-6 Weeks Exposure to Immune-Attractant

This is an open-label, multicentric, international, phase II trial testing aromatase inhibitors in combination with durvalumab in patients with CD8+ T cell infiltration (>10% CD8+ T cells in the tumor). The trial includes two sequences: The first part of the treatment will consist in 4-6 weeks treatment with immune-attractants; in the second part, CD8+ patients will receive 6 months of durvalumab combined with exemestane.

Read the detailed description

The study is conducted in 2 parts:

Part 1: lymphocyte attraction. After the screening phase, the patient will receive immune-attractant combined with exemestane for six weeks.

As immune-attractants are added over the course of the study, they will appear as subsequent appendices in the full protocol.

Up to 4 cohorts may be tested sequentially in this design until up to 240 evaluable patients have been treated.

The first cohort of patients will receive tremelimumab (3 mg/kg, single infusion) combined with exemestane (25 mg daily). In each cohort, an interim analysis will be performed after 30 patients in order to potentially stop the cohort (if less than 25% of patients present >10% CD8+ cells in the tumor after 3 weeks). If all 4 cohorts are closed and the target number of 56 patients for part 2 has not been reached, additional patients will be recruited and treated with the best performing immune-attractant treatment based on the part I results. From the moment 56 patients are included in part 2, no more patients will be entered in part 1.

After three weeks (+/- 3 days), a tumor biopsy will be done. Patients who present >10% CD8+ cells in the tumor after 3 weeks and remain eligible will be included in the second part of the trial (patients who do not present CD8+ T cells on the 3-week biopsy will be treated at the investigator's choice).

Part 2: lymphocyte activation (anti-PD1 treatment) Four to six weeks after immune-attractant start, patients having >10% CD8+ cells in the tumor will receive durvalumab 1500 mg Q4W (equivalent to 20 mg/kg Q4W) IV, combined with exemestane (25 mg daily), for six months.

Part 2 will include two steps. In the first step, we will include 23 patients. If 2 or more pathological complete responses are observed in these 23 patients, the part 2 will move to step 2. 33 additional patients will be included in the step 2.

Being tested
Immune-attractant, Durvalumab, Biopsy
Keywords
T2-T4 Breast cancer, Estrogen Receptor Positive Tumor, PD-1, Neoadjuvant, Immune-attractants, lymphocytes activation
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Immune-attractantDrug

    Also called Tremelimumab

    The first cohort patients will receive tremelimumab (3 mg/kg, single infusion) as immune-attractants combined with exemestane (25 mg daily).

  • DurvalumabDrug

    Also called MEDI4736

    Durvalumab (lymphocyte activation) will be administrated at a dose of 1500 mg Q4W (equivalent to 20 mg/kg Q4W) IV, combined with exemestane (25 mg daily), for six months

  • BiopsyProcedure or surgery

    After three weeks (+/- 3 days) of immune-attractants, a tumor biopsy will be done. Patients who present >10% CD8+ cells in the tumor after 3 weeks will receive the Durvalumab

Study groups in NCT02997995
Study groupRoleWhat they receive
Immune-attractant/lymphocyte activationExperimentalAfter the screening phase, the patient will receive immune-attractant combined with exemestane for six weeks. After three weeks (+/- 3 days), a tumor biopsy will be done. Patients who present >10% CD8+ cells in the tumor after 3 weeks and remain eligible will be included in the second part of the trial i.e. lymphocyte activation. In this second part, patients will receive durvalumab 1500 mg Q4W (equivalent to 20 mg/kg Q4W) IV, combined with exemestane (25 mg daily), for six months. The pathological response will be checked by surgery.
Receives: Drug: Immune-attractant; Drug: Durvalumab; Procedure: Biopsy

What is being measured

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

  1. pathological Complete Response

    Response at surgery

    Measured: at time of surgery

Secondary outcomes (6)

  1. Number of CD8+ T cell

    exam at biopsy and comparison between biopsy and Baseline biopsy rates

    Measured: at biopsy (3 weeks)

  2. Clinical response

    Clinical exam

    Measured: after 6 months of Durvalumab

  3. Assessment of Ki67

    measure of Ki67

    Measured: at surgery

  4. Toxicities

    Common terminology criteria for adverse events (CTC-AE) v4.03

    Measured: 1 year and 8 months

  5. Predictive value of Mutational load for efficacy of Durvalumab

    exome sequencing on baseline samples

    Measured: on baseline biopsy and blood samples

  6. Predictive value of PDL1 expression for the efficacy of Durvalumab

    correlate Immune infiltrate intensity with the proportion of tumor cells expressing PD-L1 by Ventana SP263 assay

    Measured: on baseline biopsy and biopsy at 3 weeks

Timeline

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

  1. First posted20 Dec 2016 (estimated)
  2. Study start15 Feb 2017
  3. Primary completion15 Jul 2019
  4. Study completion28 Aug 2020

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
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02997995
Sponsor's protocol ID
UC-0140/1606
Other IDs
UCBG-105, BIG 16-01, 2016-000764-42, 2016
Acronym
ULTIMATE
Status last verified
Sep 2020
First submitted
9 Dec 2016
Last updated
30 Sep 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Immune-attractant, Durvalumab and Biopsy in people with Breast Cancer and Estrogen Receptor Positive Tumor, run by UNICANCER at 29 sites in 3 countries.

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 23 inclusion and 21 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 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in France, Spain, Sweden. 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?

pathological Complete Response (time frame: at time of surgery). 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 NCT02997995.

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 30 Sep 2020.

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