GCIG Virtual Spring Meeting 2020 slide deck May 29...GCIG Virtual Spring Meeting 2020 Some rules for...

GCIG Virtual Spring Meeting 2020

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groups should send an email to the presenter

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ENDOMETRIAL CANCER COMMITTEE TUESDAY, JUNE 2, 2020

Chair: Stefano Greggi Co-Chair: Carien Creutzberg Harmonization Liaisons: Karen Verhoeven (Ops); Dongsheng Tu/Andrew Embleton (Stats)

AGENDA

Welcome and Introductions: S. Greggi COI Disclosures: Approval of Report: November 2019 (posted on GCIG website) Motion: __________________________ Seconded: _____________________________ NEW PROPOSALS/CONCEPTS: BGOG: ENGOT-EN11/KEYNOTE-B21 (Toon v Gorp) ANZGOG: EN3 (Andreas Obermair) UDATE OF TRIALS IN DEVELOPMENT: CCTG: DOMINO (Stephen Welch) DGOG/GINECO/NCRI: RAINBO (Carien Creutzberg / Judith Kroep) NCI/ANZGOG: Phase III study of carboplatin/paclitaxel alone or combined with either trastuzumab or trastuzumab/pertuzumab in HER2 overexpressing EC (Matthew Powell) ONGOING TRIALS (maximum of 5 minutes each): NCI: NRG-GY-020. A phase III random. trial of RADIATION +/- MK-3475 (Pembrolizumab) FOR newly diagnosed EARLY Stage MSI+ EC (Matthew Powell) NCI: NRG-GY-018. (Matthew Powell) BGOG: ENGOT-EN5/SIENDO (Ignace Vergote) NSGO: ENGOT-EN6-NSGO/RUBY (Mansoor Mirza) AGO: AGO-OP.6 / ECLAT (Philipp Harter) MITO: ECCO, AEC (Stefano Greggi) COGI: SAVE (David Gaffney) DGOG: PORTEC-4a (Carien Creutzberg) MANGO: AtTEnd (Nicoletta Colombo) CLOSED/PUBLISHED STUDIES: S. Greggi

Discussion/Future Directions: Experience with COVID situation in Italy and consequences for trials – Stephano Greggi ADJOURN

EN Committee, May 2020

New proposals

ENDO-3A Phase III Randomised Clinical Trial Comparing Sentinel

Node Biopsy with No Retroperitoneal Node Dissection in

Apparent Early-Stage Endometrial Cancer

A Obermair, ANZGOG

Background

Is there value to patients of SLND for the surgical treatment of Endometrial Cancer (EC)?

Practice management guidelines of EC mandate surgical assessment of lymph nodes.

Research has been focussed on technique and accuracy of SLND (“Can it replace LND for staging?”).

Patient benefit of SLND has been argued (e.g., selection of treatment, survival) but is yet to be demonstrated.

Potential of patient detriment: In FIRES 12% of patients had positive LNs but 19 of 36 patients with positive LNs had (very-) low volume involvement.

ASTEC and Italian LND trials

No benefit of DFS or OS

Incidence of adverse events 3.5 times higher for LND

ASTEC trial

Italian trial

Trial design

Trial design

Phase 3 RCT to provide definitive evidence on value of SLND

Participants receive TH BSO with SNB

Participants receive TH BSO without retroperitoneal node dissection

Primary outcome is DFS at 4.5 years

Secondary outcomes: PROMS/QoL; perioperative outcomes; adverse events; lymphoedema, adjuvant treatment; cost/cost effectiveness; molecular.

Stage 1 – 444 participants using 1:1 randomisation

Stage 2 – Further 316 participants using 1:1 randomisation

Stratification by histological cell type (endometriodvs other), treatment centre, surgical approach (lap vs robot), BMI (<30, 30-45, >45) and age.

Adjuvant treatment: Based on uterine factors and ESMO risk stratification • Positive LN will be offered chemotherapy• ITC shall not be offered chemo• Micrometastasis (<0.2 mm) clinician’s discretion

Power Calculations

Primary Outcome Measure is DFS at 4.5 years

Estimated 4.5-yr DFS rate in the control group is 90%

A non-inferiority (NI) margin of 5% at 4.5 years would be clinically worthwhile in trading off the extra morbidity associated with SLND.

A sample size of 721 participants would have 80% power with 97.5% (one-sided) confidence to detect a 5% difference at 4.5 years assuming a 4-year accrual and minimum of 4-year follow-up time.

Allowing for a modest 5% loss to follow-up, the total sample size for the study would be 760 participants. This sample size will also have >90% power to detect a NI margin of at most 6% at 4.5 years.

Quality assurance

Surgeon accreditation

Provide evidence of 30 cases

Competency Assessment Tool (CAT) developed though 4-round Delphi process)

Surgeons need to perform SLND at least twice a month

SLN detected in at last 7 of the most recent 10 cases

Continuously, all SLND cases will be video-recorded and randomly assessed (CAT)

Independent Data Safety Management Committee

Recurrence adjudication committee


Trials under development – status update

Resected stage III endometrioid endometrial cancerLND mandatory**Local d-MMR

Chemoradiotherapy*

RANDOMIZE

Stratify by:• ECOG PS• CRT regimen

*Chemoradiotherapy = Investigators’ choice (“sandwich” vs PORTEC3)**Sentinel LND allowed

CCTG Proposal: Durvalumab as part of Post-Operative Therapy for MIsmatch

Repair-deficient eNdOmetrial cancer(DOMINO)

1:1

Sample size =170 pts

Observation

Durvalumab1500 mg IV Q4W(max 12 months)

NED on CT

Contact: [email protected]

RAINBO umbrella program

Refining Adjuvant treatment IN endometrial cancer Based On molecular profile (RAINBO)

a TransPORTEC collaboration and initiativeDGOG, GINECO, NCRI, CCTG, ANZGOG

Carien Creutzberg and Judith Kroep for TransPORTEC Consortium

Vermij et al; Histopathology 2020

MMR proficientMMR deficient

p53 normal p53 abnormal

POLE pathogenic POLE wildtype or non-pathogenic POLE variant

EEC, NOSSEC, NOSCCC, NOSDEC, NOS

POLEmut EC MMRd EC NSMP EC p53mut EC

Endometrial CancerEndometrioid, Serous, Clear Cell, Dediff EC

Molecular testing notperformed OR inconclusive

Surrogate Marker Tests:

1. POLE sequencing

2. MMR-IHC

3. p53-IHC

Paradigm Shift in Endometrial Cancer Classification

PORTEC-3Molecular analysis successful in 97% of

samples

Molecular classification prognostic

PORTEC-3 HR-EC trial cohort N=410

32% NSMP

33% MMRd13% POLE

22% p53

Stelloo et al, Clinical Cancer Research 2016; Leon-Castillo et al, ESMO 2019; **Leon-Castillo et al, J Pathol 2020

Double classifiers reclassified**

N=410 (PORTEC-3)

POLE

NSMP

p53abn

MMRd

p=0.015, HR 0.50 (95%CI 0,28-0,88)

Creutzberg, Leon-Castillo et al, ESMO 2019 and Leon-Castillo et al, ESGO 2019

PORTEC-3

Molecular classification predictive of differential benefit from adj Ctx

p53abnPOLEmut MMRd NSMP

• P53abn: worst prognosis but greatest benefit from adj Ctx• POLEmut: does not relapse regardless of tx• MSI and NSMP: intermediate prognosis , but little benefit from Adj Ctx

No adj tx needed? Adj IO rather thanCtx?PARP as

maintenance?

• International program of personalized, molecular based, adjuvant treatment of pts with HREC to increase 5-yr RFS with less toxicity

• Patients will be centrally registered and after molecular classification be recruited into the international program and be allocated to one of the four subtrials: p53abn, MMRd, NSMP and POLEmut.

• Groups involved: DGOG, GINECO, NCRI, CCTG/PMH, ANZGOG

• Groups interested: ENGOT, EORTC, SAKK, CEEGOG, ….?

RAINBO: Refining Adjuvant treatment INendometrial cancer Based On molecular features

RAINBO: Refining Adjuvant treatment INendometrial cancer Based On molecular features

RAINBOSteering Committee*

RAINBOAdvisory Committee*

transPORTEC RAINBO Consortium

PI: Dr. A. LearyGINECO

PI: Dr. J. KroepDGOG

PI: Dr. M. PowellNCRI

PI: Dr. H. Mackay / K. HanCCTG/PMH

RAINBO PIs

RAINBOTranslational Research

Committee*

*RAINBO committees will include international experts on endometrial cancer management, oncologists, radiation oncologists, pathologists, statisticians and patient advocacy

Resected ECAll histologic subtypes

MolecularClassification

RAINBO umbrella program supported by GCIG and coordinated by TransPORTEC will allocate EC pts to 4 international academic sub-trials each led by one Gyn-Onc national clinical trial group

RCT/RT → PARPinhib

CT/RT

R

RT → aPD1

RT (RTCT for stage III allowed)

No Adj Tx

RRT → Hormonal Tx

CT/RT

RAINBO umbrella Program

N = 485GINECO

N = 300DGOG

N = 698NCRI

N = 100CCTG/PMH

Primary endpoint 5-yr RFS

RAINBO – protocol design and funding

RCT/RT → PARPinhib

CT/RT

R

RT → aPD1

RT (RTCT for stage III allowed)

No Adj Tx

RRT → Hormonal Tx

CT/RT

N = 485GINECO

N = 300DGOG

N = 698NCRI

N = 100CCTG/PMH

Protocol development ongoingAcademic trialsPharma support likelyCombined with DCS grant applicationCancer Research UK grant application

TAPER de-escalation trial

TAPER trial POLE (and p53wt) Trial – single arm

Inclusion criteriaEndometrial endometrioid adenocarinoma

Stages IA G3, IB, II (microscopic)POLEmut & p53wt EC

No adjuvant treatment for POLEmutDe-escalation of RT for p53wt

PI team : Canada – Han/McAlpine//Fyles/Mackay/WelchAim: Confirm safety of no additional or de-escalated treatment in POLEmut & p53wt ECPrevalence: POLEmut ~5-10% of EC; p53wt ~50%Single arm prospective phase II trial – assumption 3-year pelvic relapse < 4% - stopping rule when ≥ 4% relapse (2-stage design)

N= 276

Follow-up

Exclusion criteriaNon-pathogenic POLEmutMMRd, p53 abn

NRG UC1972HER2+ Serous Carcinomas

Trial setting: HER2 positive stage I-IV uterine serous carcinoma and

carcinosarcoma after primary surgery

Study Design: 3 Arm Randomized phase III trial carboplatin/paclitaxel

alone or combined with either trastuzumab or

trastuzumab/pertuzumab ;

Endpoints: primary: PFS Secondary: OS, RR, safety / tolerability

Sponsor(s): NCI

Planned No. of patients: 347

Current accrual: 0

Other important: Study design and inclusion in development

Proposed Trials – status update

NRG UC1972BACKGROUND- Breast/Gastric

• 15% of breast cancer HER2+ & US FDA approved Trastuzumab (T) in 1998

• HERA trial enrolled over 5,000 women early stage: One year of maintenance

DFS(HR 0.76, 95% CI 0.68-0.86) and death (0.74, 0.64-0.86). 10 year survival

improvement from 63% to 69%; two years maintenance did not improve

• Meta-analysis 1,400 patients with HER2-positive metastatic breast cancer, the

addition of T improved OS (HR 0.82, 95% CI 0.71-0.94) (Balduzzi 2014).

• Gastric cancer: ORR 35% to 47% and OS significantly improved with T (13.8

versus 11.1 months, HR 0.74, 95% CI 0.60-0.91).

• Pertuzumab (P) binds dimerization domain, inhibiting HER2 to other HER family

receptors (heterodimerization). Approved in MBC and EBC with APHINITY trial

n=4,804 HER2-positive early breast cancer: T+chemo +-T. DFS 7.1% with P and

8.7% in the placebo group (HR 0.82, P = .047).


NRG UC1972BACKGROUND- RP2 trail

• RP2 Fader et al: randomized 61 patients 1:1 to receive carboplatin/paclitaxel

for 6 cycles ± trastuzumab followed by maintenance trastuzumab until

progression or toxicity.

• Benefit appeared to be primarily in the newly diagnosed patients (Stage III/IV)

PFS (9.0 versus 14.8 months, HR 0.393, 90% CI 0.203-0.758, p=0.0078)

OS (21.1 versus 31.9 months, HR 0.440 90% CI 0.219-0.882 p=0.0230)


17 4 3 3 3 3 2 0

19 14 7 5 4 2 0

0 12 24 36 48 60 72 84

Months since on-treatment date

0.0

0.2

0.4

0.6

0.8

1.0

Pro

port

ion p

rogre

ssio

n-fre

e

NoYes

YesNoTrastuzumab

PFS vs Trastuzumab, Advanced (IIIC or IV)With Number of Subjects at Risk

17 4 3 3 3 3 2 0

19 14 7 5 4 2 0

0 12 24 36 48 60 72 84

Months since on-treatment date

0.0

0.2

0.4

0.6

0.8

1.0

Pro

port

ion p

rogre

ssio

n-fre

e

NoYes

YesNoTrastuzumab

● Censored

PFS vs Trastuzumab, Advanced (IIIC or IV)With Number of Subjects at Risk

17 13 8 3 3 3 2 0

19 19 14 7 6 4 0

0 12 24 36 48 60 72 84

Months from on-treatment date

0.0

0.2

0.4

0.6

0.8

1.0

Pro

port

ion A

live

NoYes

YesNoTrastuzumab

Overall Survival vs Trastuzumab, Advanced (IIIC or IV)With Number of Subjects at Risk

17 13 8 3 3 3 2 0

19 19 14 7 6 4 0

0 12 24 36 48 60 72 84

Months from on-treatment date

0.0

0.2

0.4

0.6

0.8

1.0

Pro

port

ion A

live

NoYes

YesNoTrastuzumab

● Censored

Overall Survival vs Trastuzumab, Advanced (IIIC or IV)With Number of Subjects at Risk

NRG UC1972BACKGROUND

Inclusion of Carcinosarcomas (UCS)?

• UCS frequently contains serous components and in a recent TCGA study, 78%

of the samples were considered “serous like” based on molecular analysis

(Cherniack et al). Serous histology drives outcome (Gotoh, Nature, 2019)

• UCS overexpress HER2: 13 of 80 patients (16%) were HER2 positive based on

IHC or FISH testing. All 13 of the positive cases had either serous or mixed

carcinoma component (Rottman et al, 2020).

• Targeting HER2 in vitro and in vivo had been demonstrated in UCS models, with

strong anti-tumor effects (Menderes et al).

• Carboplatin and paclitaxel is now considered the standard of care for all stage

of UCS (GOG 0261;Powell et al, ASCO 2019).



Inclusion of Early Stage?

• Treatment is controversial; Portec3 suggest ChemoRT; GOG258: serous I/II +cytology

• Her2 appears to be an important predictive biomarker for early stage serous patients:

• Erickson et (ASCO 2020): n=169; 44 (26%) were HER2+ and 125 (74%)HER2- neg

• Despite chemotherapy: 43 patients (25.4%) experienced relapse and HER+ tumors

were more likely to recur (50% vs 16.8%, p<0.001)

• Multivariate analysis, HER2+ was a strong independent risk factor for recurrence (aHR

3.50, 95% CI 1.84 – 6.67, p <0.001) and OS (aHR 2.00, 95% CI 1.04 – 3.88, p = 0.039)


• All patients must have tumors that are HER2 positive as defined by ASCO/CAP 2018 guidelines (3+ IHC, 2+ IHC with positive FISH, or FISH positive) – Centralized pre-testing versus local testing with conformation??

• Sample size: PFS

• Concern about accrual

Given wide spread us of T in

USA for advanced staged

115 patients per arm:

-10/mo accrual time 35 mo


Other considerations…


0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44

Prop

ortio

n Al

ive

With

out P

rogr

essio

n

Months from Randomization

Estimated PFS Distributions in the Reference Arm

Overall Early Stage Advanced Stage

Early Stage

OVERALL

Advanced Stage


Ongoing Trials – status update

NRG GY-018

Trial setting: Measurable Stage III or IVA, Stage IVB or Recurrent

Endometrial Cancer

Study Design: A Phase III Randomized, Placebo-Controlled Study

Paclitaxel and Carboplatin +- Pembrolizumab to progression or 2 years

Sponsor(s): NCI (A)

Planned No. of patients: N: 590 pMMR; 220 dMMR = 810

Current accrual: 94

Other important: Centralized MMR/MSI testing.


NRG GY-018


NRG GY-020

Trial setting: High intermediate risk mismatch repair deficient (dMMR)

endometrioid endometrial cancer

Study Design: Randomized phase III trial of radiation +/-

pembrolizumab

Primary outcome: 3-year RFS

Sponsor(s): NCI (A)

Planned No. of patients: N: 168 (2:1 randomization)

Current accrual: 4

Other important: Considering addition of non-measurable stage III

patients.


PENDING:

NRG GY-020

- Arm 1: vaginal brachytherapy or pelvic radiation- Arm 2: vaginal brachytherapy or pelvic radiation with MK-3475

(pembrolizumab) every 3 weeks x 1 year (**Proposed amendment proposed to change to 400mg q 6 weeks)

- All patients will receive standard vaginal brachytherapy

- For patients with Stage IB grade 3 (≥ 50% myometrial invasion and grade 3) or Stage II, the treating physician may choose to prescribe pelvic external beam radiation (EBRT). This must be decided prior to randomization. All other patients will receive vaginal brachytherapy only


PENDING:

NRG GY-020

• Stage I endometrioid endometrial cancer and a combination of age and risk factors:

- Age >70 and ≥1 risk factor- Age 50-70 and 2 risks factors- Age <50 and 3 risk factorsRisk factors: - Myometrial invasion ≥ 50%

- Lymphovascular space invasion- Grade 2 or 3

• Stage II endometrioid endometrial cancer • Patients with isolated tumor cells in sentinel lymph nodes are

eligible (considered N0i) as long as there is no evidence of micro-or macro-metastases in any lymph nodes.


PENDING:

Key Eligibility Criteria

ENGOT-EN6 /NSGO - RUBY

Eligible SubjectsRecurrent or PrimaryAdvanced (stage III or IV) Endometrial Cancer or first recurrent endometrial cancer with a low potential for cure by radiotherapy or surgery alone or in combination

N = 470Randomization 1:1

Dostarlimab 500 mgCarboplatin AUC5mg/mL/minPaclitaxal 175 mg/m2

Q3W for 6 cycles

Dostarlimab 1.000 mgQ6W up to 3 years*

Follow-up

Stratification:

By microsatellite instability (MSI) status (MSI-high [MSI-H] or microsatellite stable [MSS]), prior external pelvic radiotherapy (yes or no), and disease status (recurrent, primary Stage III, or primaryStage IV).

PlaceboCarboplatin AUC5mg/mL/minPaclitaxal 175 mg/m2

Q3W for 6 cycles

PlaceboQ6W up to 3 years*

*Treatment ends after 3 years, progression of disease, toxicity, withdrawal of consent, Investigator’s decision, or death, whichever occurs first. Continued treatment with dostarlimab or placebo beyond 3 years may be considered following discussion between the Sponsor and the Investigator.

Principal Investigator: Mirza

Sponsor: Tesaro-GSK

Lead Group: NSGO

ECLAT - Endometrial Cancer

Lymphadenectomy Trial

AGO-OP.6

For further information, please contact: Philipp Harter ([email protected])

R

System. lymphadenectomy

⚫ pelvic

⚫ para-aortic

No lymphadenectomy

• histologically confirmed

endometrial cancer

• FIGO IB or FIGO II

(all subtypes)

• FIGO IA, G3 (Type I)

• FIGO IA (Type II)

• Absence of bulky nodes

• Age 18 - 75y

n=640

SLN in LNE arm as additional procedure allowed

Primary endpoint:

Overall Survival

Type I: endometrioid, endometrioid + squamous differentiation,

mucinous

Type II: serous, clear cell, carcinosarcoma

mailto:[email protected]

• Trial Model: Academic (A)

• Sponsor: Philipps-University Marburg / AGO Study Group

• Trial status: Recruiting

• Planned accrual: 640 patients in 5 years

• Current accrual: 173 patients randomized (Status May 14th, 2020)

• GCIG Groups involved: AGO, NOGGO, KGOG

Further groups are invited to join

• Other important information: None

ECLAT - Endometrial Cancer

Lymphadenectomy Trial

AGO-OP.6

E.C.Co. Endometrial Cancer Conservative treatment

A multicentre archive

Data collection is made by appropriate eCRFs via the Clinical Trials Unit of

National Cancer Institute of Naples (Study Data Center) website

PROJECT TYPE / DESIGN & TIME PERSPECTIVE

Observational / Patient archive, Prospective (a first phase of three years is planned, eventually followed by

further three years)

INCLUSION CRITERIA

- Conservatively treated endometrial cancer

- Informed consent to personal data processing

- Existence of an IRB-approved local protocol that allows conservative treatment to be performed (or statement

that such treatment is considered as a standard)

INTERVENTIONS & OUTCOME MEASURES

Data collection - PRIMARY OUTCOME MEASURES: proportion of complete regression, duration of response,

frequency and pattern of relapse, frequency of metachronous ovarian cancer, tumor-related deaths; SECONDARY

OUTCOME MEASURES: treatment related morbidity, frequency of spontaneous pregnancies, frequency of

pregnancies after ART, pattern of residual disease on definitive surgical specimens

TREATMENT

SINCE THIS IS A ARCHIVE, TREATMENT IS NOT DICTATED BY A PROTOCOL, HOWEVER, TREATMENT HAS TO BE

ADMINISTERED ACCORDING TO A IRB-APPROVED LOCAL PROTOCOL (except for the countries where conservative

treatment can be given outside a IRB-approved study because considered as a standard procedure)



Country Sites PI #pts registered

Naples, NCI Greggi S. 33

Rome, Catholic University Scambia G 19

Avellino, Malzoni Center Malzoni M. 10

Wien, University Polterauer S. 9

Milan, NCI Raspagliesi F. 7

Bergamo, ‘Papa Giovanni XXIII’ H Malandrino C. 6

Milan, ‘S. Raffaele’ H De Marzi P. 4

Naples, Ist University Zullo F. 3

Bari, ‘Giovanni Paolo II’ H Cormio G. 3

Parkville, Royal Women's H - 1

Fudan, University Chen X. -

Leiden, University - -

Rome, NCI Vizza E. -

Varese, F. Del Ponte H Ghezzi F. -

95

Participation (11.05.2020)





Fertility-sparing treatment for intramucous, moderately differentiated, endometrioid endometrial cancer:

A Gynecologic Cancer Inter-Group (GCIG) study

In press, Journal of Gynecologic Oncology (accepted, May 25, 2020)

Falcone F, Leone Roberti Maggiore U, Di Donato V, Perrone AM, Frigerio L, Bifulco G, Polterauer S, Casadio P, Cormio G, Masciullo V, Malzoni M, Greggi S

(Analysis on 23 patients)

CONTACT INFORMATION

STEFANO GREGGI, MD, PhD

Gynecologic Oncology Surgery,

Istituto Nazionale Tumori “Fondazione G. Pascale”

Via M. Semmola, 80131, Naples, Italy

Tel.: +39 0815903320; Fax: +39 0815903851

E‐mail: [email protected]



Cytoreductive Surgery in Advanced Endometrial Cancer

Multicenter Retrospective Study

Ongoing Trial – status update

Objectives

To explore the feasibility of a biomolecular grouping analysis (ProMisE

molecular classifier)*

*potential subsequent prospective phase to validate

To document the treatment strategy adopted in oncology reference

centers for patients with primary AEC;

To identify the predictors of survival;

To formulate a hypothesis for selection criteria/predictive factors for

successful CRS in AEC;

1

2

3

4







Eligibility

Patients with primary advanced endometrial cancer

treated during the period 2005 – 2015

Inclusion criteria

FIGO Stage: IIIA bulky*; IIIB; IIIC1 bulky*; IIIC2 bulky*; IVA; IVB intraabdominal

* diagnosed by pre-operative imaging techniques and/or intraoperatively

Exclusion criteria

- Age > 75;

- Performance Status (ECOG) >1;

- Patients treated for strictly palliative purposes;

- Patients with second malignancies who had been treated by laparotomy or

who had a therapy that could interfere with the treatment of AEC




Participating site status 11.05.2020




Country Sites Group Recruitment # pts registered

Naples, NCI MITO Active 35

Bari, NCI MITO Active 57

Parkville, The Royal Women's Hospital ANZGOG Active 17

Torino, S. Anna H MITO Active 16

Reggio Emilia, ‘S. Maria Nuova’ H MITO Active 15

Rome, S. Giovanni Addolorata H MITO Active 14

Herston, RBWH and Wesley H ANZGOG Active 8

Trieste, ‘Burlo Garofolo’ H MITO Active 7

Naples, Ist University MITO Active 1

Avellino, Malzoni Center MITO Active 0

Varese, F. Del Ponte H MITO Active 0

Bern, University SAKK Active 0

Bergamo, ‘Papa Giovanni XXIII’ H MITO Active 0

Milan, ‘S. Raffaele’ H MITO Active 0

Subiaco, St John of God Subiaco H ANZGOG Active 0

Westmead H ANZGOG Active 0

Fudan, University SGOG pending -

170

Contact Information

STEFANO GREGGI, MD, PhD

Gynecologic Oncology Surgery,

Istituto Nazionale Tumori di Napoli IRCCS “Fondazione G. Pascale”

Tel.: +39 0815903320; Fax: +39 0815903851

E‐mail: [email protected]




Study package available on

http://www.usc-intnapoli.net

2 Fractions11 Gy at the surface

(7.3 Gy at ½ cm for a 3 cm cylinder)

Standard of care brachytherapy1. 7 Gy @ ½ cm x 32. 5-5.5 Gy @ ½ cm x 43. 6 Gy @ surface x 5

Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) in Early Endometrial Cancer Compared to Standard of Care (SAVE)

•Primary Objective:•Evaluate patient reported outcomes (PROs) using the Global Health Score from the QLQ30

•Secondary Objectives: •Evaluate cost effectiveness •Evaluate CTCAE v4 toxicities•Document any pattern of recurrence

Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) in Early Endometrial Cancer Compared to Standard of Care (SAVE)

53/108 accrued

PORTEC-4a

Trial setting: Stage I-II endometrial cancer - high-intermediate risk

Study Design: Randomised trial of molecular profile-based versus standard recommendations for adjuvant radiotherapy

Sponsor(s): LUMC; funding: Dutch Cancer Society


Current accrual: 212

Other important information: International participation : Belgium (Univ hospGhent), Germany (Tübingen, München, Essen, Lubeck), Cancer Trials Ireland; CEEGOG Prague; GINECO preparing activation; Vienna preparing activation


Inclusion criteria: FIGO 2009 – high intermediate risk endometrial cancer

• Stage IA (with invasion), any age with grade 3 • Stage IB, grade 1-2 and age > 60• Stage IB, grade 1-2 and LVSI+• Stage IB, grade 3 without LVSI• Stage II (microscopic), grade 1

PORTEC-4a


2 1 Standard treatment recommendation based on clinicopathological factors

Vaginal brachytherapy

Vaginal brachytherapy (~40%)

Observation (~55%)

External beam radiation therapy (~5%)

Follow-up and Quality of Life

Randomisation

Favourable

Intermediate

Unfavourable

Individual treatment recommendation based on

molecular pathology analysis

PORTEC-4a


Pilot phase (n=50) endpoints:

• Logistics of molecular analysis (< 2 wks)

• Patient acceptance

• Completed: 50 pts

PORTEC-4a study endpoints (n=500):

• Vaginal control and RFS

• Pelvic and distant recurrence and OS

• Quality of life and freedom from symptoms

• Costs and use of health care resources

• Current total: 327

➢ Requirement to determine profile within 2 working weeks➢ Participating groups: validation of molecular profile & logistics;

dummy run & QA procedure for brachytherapy

➢ Some delay in accrual due to COVID-19

Trial model: academic

Sponsor(s): MaNGO - Istituto di Ricerche Farmacologiche Mario Negri IRCCS - Milan

Principal Investigator: Nicoletta Colombo, Istituto Europeo di Oncologia - Milan


Paclitaxel 175mg/m2

carboplatin AUC 5 or 6 placebo

Maintenance placebo

Paclitaxel 175mg/m2

carboplatin AUC 5 or 6 atezolizumab 1200mg

Maintenance atezo 1200mg

Stage III/IV with residual disease or

recurrent endometrialcancer

Confirmed PD

R 1:2

Stratified by:

▪ Country

▪ Histological type

▪ Disease (recurrent disease vs advanced disease at primary

diagnosis)

▪ MS status

AtTEnd - Atezolizumab Trial in

Endometrial cancer

AtTEnd - Study Update

As of 22 May 2020

number of randomized patients: 183• Trial status: recruiting

• Accrual start: October 2018

• GCIG involved groups:

A-AGO, AGO, SAKK, NCRI,

JGOG, GEICO, ANZGOG

• Involved sites: 94

• Active sites: 62

• ANZGOG sites will be

opened by June 2020


Closed Trials – status update

ENGOT-EN1/FANDANGO - Trial DesignA randomised double-blind placebo-controlled phase II trial of first line combination chemo-therapy

with Nintedanib/placebo for patients with advanced or recurrent endometrial cancer.

Stratification:• Stage of disease (stage 3C 2 vs. stage 4 vs. recurrent disease) • Prior adjuvant chemotherapy (yes/no) • Disease status (Measurable vs. non-measurable disease according to RECIST

1.1)

Ran

do

miz

atio

n 1

:1N

= 1

48

Primary end-point:Progression-Free Survival (PFS)

ENGOT model: A

Status: Randomization closedLast patient randomized: 25.01.2019Sponsor: NSGO-CTUNSGO-CTU PM: Mette Engell

Primary Endpoint (PFS) expected:

2021

ENGOT-EN2-DGCG - Trial DesignA phase II Trial of postoperative chemotherapy or no further treatment for patients with node-

negative stage I-II intermediate or high-risk endometrial cancer.

Supported by

n=240

Endometrioid:Stage I - G3; II

Non-endometrioid:Stage I-II

ChemotherapyCarboplatin-Paclitaxel x 6+ BrachytherapyObservation+ Brachytherapy

1:1 randomization

ENGOT model: A

Status: Randomization closedLast patient randomized: 23.04.2019Sponsor: DGCGNSGO-CTU PM: Joan Løhndorf

Primary end-point:Overall survival (OS)

Primary Endpoint (OS) expected:

2022/2023

Endometrial Cancer

Primary stage 4 or relapsed disease

ER positive endometrioid

adenocarcinoma

Randomize

Randomization: 1:1

N=78

ARM ALetrozole, 2.5mg d 1-28 every 28 daysPlacebo 125mg d 1-21 every 28 days

Until progression

ARM BLetrozole, 2.5mg d 1-28 every 28 days

Palbociclib 125mg d 1-21 every 28 days

Until progression

Stratification:• Number of prior lines (primary adv disease vs. 1st relapse vs. ≥2 relapses)• Measurable vs. evaluable disease• Prior use of MPA/Megace

ENGOT-EN3/NSGO-PALEO - Trial DesignA randomized, double-blind, placebo-controlled, phase II trial of Palbociclib in combination with Letrozole versus

Placebo in combination with Letrozole for patients with Estrogen Receptor Positive advanced or recurrent Endometrial

cancer.

ENGOT model: A

Status: Randomization closedLast patient randomized: 21.12.2018Sponsor: NSGO-CTU NSGO-CTU PM: Joan Løhndorf

Primary end-point: Progression-Free Survival (PFS)

Primary Endpoint (PFS):

ESMO 2020

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