Clinical Trials Register

Summary
EudraCT Number:	2018-002155-15
Sponsor's Protocol Code Number:	GEICO78-C
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-05-27
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2018-002155-15

A.3

Full title of the trial

A randomized, open label, phase II trial of Anti-PD1, TSR-042, as maintenance therapy for patients with high-risk locally advanced cervical cancer after chemo-radiation

Ensayo aleatorizado, fase II, abierto, con el anti-PD1 TSR-042 como terapia de mantenimiento en pacientes con cáncer de cérvix localmente avanzado de alto riesgo después de quimioradioterapia

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Trial of TSR-042 for patients with high-risk locally advanced cervical cancer after chemo-radiation

Ensayo con TSR-042 en pacientes con cáncer de cérvix localmente avanzado de alto riesgo después de quimioradioterapia

A.4.1

Sponsor's protocol code number

GEICO78-C

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Grupo Español de Investigación en Cáncer de Ovario (GEICO)
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	TESARO
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	APICES
B.5.2	Functional name of contact point	Ana Maria Moreno Fernandez
B.5.3	Address:
B.5.3.1	Street Address	Avenida Antonio Lopez 16 1A
B.5.3.2	Town/ city	Pinto
B.5.3.3	Post code	28320
B.5.3.4	Country	Spain
B.5.4	Telephone number	34918166804100
B.5.5	Fax number	34918169172
B.5.6	E-mail	ana.moreno@apices.es

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	TSR-042
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TSR-042
D.3.9.2	Current sponsor code	TSR-042
D.3.9.3	Other descriptive name	TSR-042
D.3.9.4	EV Substance Code	SUB181448
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cervical cancer

Cancer de cérvix

E.1.1.1

Medical condition in easily understood language

Cervical cancer

Cancer de cérvix

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10008229
E.1.2	Term	Cervical cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the progression-free survival (PFS) of patients with high risk locally advanced cervical cancer (HRLACC) who have achieved a partial (PR) or complete response (CR) after concurrent chemotherapy and radiation therapy (CCRT) and received TSR-042 as maintenance therapy.

E.2.2

Secondary objectives of the trial

- Determine the frequency and severity of adverse events (AEs) as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for TSR-042 administered on this study.
- Evaluate the overall survival (OS) of subjects with HRLACC who have received TSR-042 in the maintenance setting following concurrent chemotherapy and radiation therapy.
- Evaluate patient reported outcomes (PROs) of:
o Health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) and EQ-5D-5L,
o Fatigue as measured by the PROMIS-Cancer-Fatigue Short Form 4a, and
o Pain as measured by a single item of the Brief Pain Inventory (BPI).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent before any study-specific procedure.
2. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
3. Participant must be a female ≥ 18 years of age.
4. Life expectancy ≥3 months.
5. Participant must have biopsy-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix.
6. Patients must have archival tumor tissue available that is formalin-fixed and paraffin embedded.
7. At diagnosis:
• FIGO stages IB2, IIA2, IIB with pelvic lymph node involvement.
• FIGO stages IIIA, IIIB, IVA.
• Any FIGO stage with para-aortic lymph node involvement
8. Subjects must have received combination chemotherapy and radiotherapy (CCRT) with curative intent. Patients must have received at least 4 doses of weekly cisplatin.
9. Patients must had achieved a partial (PR) or a complete response (CR) after concurrent chemo-radiation therapy (CCRT).
10. Patients must have completed definitive treatment, namely chemo-radiation, up to 12 weeks prior to sign the Informed Consent form.
11. Toxicities resulting from chemo-radiation must resolve to ≤ Grade 1 prior to randomization.
12. Participant must have adequate organ function, defined as follows:
- Absolute neutrophil count ≥ 1,500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9 g/dL
- Serum creatinine ≤ 1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN
- Total bilirubin ≤ 1.5× ULN OR direct bilirubin ≤ 1× ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN
- International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN. Activated partial thromboplastin time (aPTT) ≤1.5× ULN
13. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
14. Negative Test Results for Hepatitis
15. Female participant has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 150 days after the last dose of study treatment, or is of nonchildbearing potential.
16. Participant must agree to not breastfeed during the study or for 150 days after the last dose of study treatment
17. Male partners must agree to use an adequate method of contraception starting with the first dose of study treatment through 150 days after the last dose of study treatment.
18. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.

E.4

Principal exclusion criteria

1. Histological types other than in inclusion criteria, like sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers
2. FIGO Stage IVB
3. Subjects who have undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy.
4. Has not achieved at least a partial response by RECIST v1.1 after completion of CCRT administered with curative intent.
5. Patients previously treated with chemotherapy except when used concurrently with radiation therapy.
6. Prior treatment with any anti-VEGF drug, including bevacizumab, CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
7. Patients with a concomitant malignancy other than non-melanoma skin cancer.
8. History of autoimmune disease
9. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
10. History of interstitial lung disease.
11. Active tuberculosis.
12. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
13. Administration of a live, attenuated vaccine within 14 days before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
14. Treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.
15. Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1.
16. Women that are breastfeeding or pregnant.
17. Demonstration of any other disease, neurological or metabolic dysfunction, found upon physical examination or laboratory tests involving a reasonable suspicion of the existence of a disease or condition that contraindicates the use of an experimental drug, or that involves an increased risk to the patient of treatment-related complications.
18. No medical or psychiatric illness that may impede the performance of a systemic or surgical treatment.
19. Participant must not be simultaneously enrolled in any interventional clinical trial.
20. Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
21. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
22. Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
23. Participant must not have a known hypersensitivity to TSR-042 components or excipients.
24. Participant must not have a serious, uncontrolled medical disorder or nonmalignant systemic disease.
25. Participant must not have known, symptomatic brain or leptomeningeal metastases.
26. Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
27. Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies).

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS)

Supervivencia Libre de Progresion (SLP)

E.5.1.1

Timepoint(s) of evaluation of this end point

First documentation of disease progression or death due to any cause, whichever occurs first.

En la primera documentación de Progresión de la enfermedad o en el fallecimiento por cualquier causa, lo que ocurra primero.

E.5.2

Secondary end point(s)

• Overall survival (OS)
• Health-related quality of life (HRQOL) measure by the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) and EQ-5D-5L.
• Fatigue measure by the PROMIS-Cancer-Fatigue Short Form 4a.
• Pain measure by a single item of the Brief Pain Inventory (BPI).

- Supervivencia global
- Calidad de vida relacionada con la salud (health-related quality of life (HRQOL)) medida mediante los cuestionarios Evaluación Funcional de la terapia fente al Cáncer de Cérvix (Functional Assessment of Cancer Therapy-Cervix (FACT-Cx)) y EQ-5D-5L
- Fatiga medida mediante PROMIS-Cáncer-Formulario Corto de Fatiga 4ª (PROMIS-Cancer-Fatigue Short Form 4ª)
- Dolor medido mediante un único elemento del Cuestionario Breve del Dolor (Brief Pain Inventory (BPI)).

E.5.2.1

Timepoint(s) of evaluation of this end point

• At the death of the patient due to any cause.
• Every 3 cycles and at the end of treatment visit
• Every 3 cycles and at the end of treatment visit
• Every 3 cycles and at the end of treatment visit

- Al fallecimiento del paciente por cualquier causa
- Cada tres ciclos de tratamiento y a la finalización del estudio
- Cada tres ciclos de tratamiento y a la finalización del estudio
- Cada tres ciclos de tratamiento y a la finalización del estudio

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Sin Tratamiento

No further treatment

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

UVUP

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

132

F.4.2

For a multinational trial

F.4.2.1

In the EEA

132

F.4.2.2

In the whole clinical trial

132

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Ninguno

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-05-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-05-08

P. End of Trial
P.	End of Trial Status	Ongoing

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