Agnostic Therapy in a Phase Ii, Multicenter, Single-Arm Study in First-Line Treatment of Durvalumab (Medi 4736) in Association with Carboplatin or Cisplatin and Etoposide in Patients Affected by Extensive Stage - Extrapulmonary Small Cell Carcinoma (Epscc) – Durvascc Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GOIRC Gruppo Oncologico Italiano Di Ricerca Clinica

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Jan 2024 → ongoing

Decision date (initial)

2023-12-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AstraZeneca spa

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the preliminary efficacy in terms of 12 months progression free survival (PFS) of durvalumab in association with carboplatin or cisplatin and etoposide in first line patients affected by extensive stage ‐EPSCC.

Secondary objectives 6

1. To evaluate the clinical activity in terms of Objective Response Rate (ORR)
2. To measure the Disease Control Rate (DCR)
3. To assess the overall survival (OS)
4. To measure the duration of response (DOR)
5. To describe change in quality of life (QoL) of patients during the study
6. To evaluate the Safety profile of durvalumab in in association with carboplatin or cisplatin and etoposide

Conditions and MedDRA coding

EXTENSIVE STAGE ‐ EXTRAPULMONARY SMALL CELL CARCINOMA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Age ≥ 18 years on day of signing informed consent.
2. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol‐related procedures, including screening evaluations.
3. Histologically or cytologically confirmed extensive disease extrapulmonary small cell carcinoma.
4. Brain metastases; must be asymptomatic or treated and stable off steroids and anti‐convulsant for at least 1 month prior to study treatment. Patients with suspected brain metastases at screening should have a CT/MRI of the brain prior to study entry.
5. No prior exposure to immune‐mediated therapy, including durvalumab excluding therapeutic anticancer vaccines.
6. No prior exposure to chemotherapy for advance disease.
7. Performance status of 0 or 1 on the ECOG Performance Scale.
8. Life expectancy ≥12 weeks at enrollment (day 1).
9. Patients must be considered suitable to receive a platinum‐based chemotherapy regimen as first‐line treatment for ES‐EPSCC.
10. Adequate organ and marrow function, all screening labs should be performed within 14 days of treatment initiation: a. Haemoglobin ≥9.0 g/dL b. Absolute neutrophil count (ANC) ≥1.0 × 109 /L c. Platelet count ≥75 × 109/L d. Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). <> e. AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which f. case it must be ≤5x ULN
11. Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft‐ Gault formula.
12. Availability of an archived tumor tissue block at baseline.
13. Evidence of post‐menopausal status or negative urinary or serum pregnancy test for female premenopausal patients.
14. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with CT o MRI, suitable for repeated measurements as per RECIST 1.1 criteria.
15. Body weight >30 kg

Exclusion criteria 15

1. Subjects with active, known or suspected autoimmune disease requiring systemic treatment (systemic steroids or immunosuppressive agents) prior 14 days before the first dose of durvalumab. 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 to exceed 10 mg/day of prednisone or its equivalent.  Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).  Premedication with steroids for chemotherapy is acceptable
2. Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
3. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non‐cancer‐related conditions (eg, hormone replacement therapy) is acceptable.
4. Any history of radiotherapy prior to systemic therapy. Radiation therapy for palliative care (ie, bone metastasis) is allowed but must be completed before first dose of the study medication.
5. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis with the exception of diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, and uveitis, etc]). The following are exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with hypothyroidism (eg, following Hashimoto syndrome) and stable on hormone replacement • Any chronic skin condition that does not require systemic therapy • Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician • Patients with celiac disease controlled by diet alone
6. Major surgical procedure within 28 days prior to the first dose of investigational product. Local surgery of isolated lesions for palliative intent is acceptable.
7. History of leptomeningeal carcinomatosis.
8. History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
9. Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
10. Receipt of live, attenuated vaccine within 30 days prior to the first dose of investigational product. Patients, if enrolled, should not receive live vaccine whilst receiving the investigational product and up to 30 days after the last dose of investigational product.
11. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
12. History of allogenic organ transplantation.
13. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
14. Female patients with a positive pregnancy test at enrollment or prior to administration of study medication
15. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy (for more information, refer to paragraph 10.8) .

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS is defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first.

Secondary endpoints 6

1. ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1.
2. DCR is measured as the percentage of patients who have achieved CR, PR and stable disease (SD)
3. OS is defined as the time from initiation of study treatment to death from any cause.
4. DOR is defined as the time from initial response to disease progression or death among patients who have experienced a CR or PR (unconfirmed) during the study. Duration of response will be calculated based on disease status evaluated by the investigator according to RECIST v1.1.
5. QoL is measured as pre‐defined PRO endpoints in this study are mean change from baseline in EORTC QLQ‐C30 questionnaire administered at the enrollment time (baseline) and after the induction phase (3± 2 weeks).
6. Safety will be evaluated in terms of incidence, nature, frequency and severity of Adverse Events (AEs) and laboratory abnormalities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GOIRC Gruppo Oncologico Italiano Di Ricerca Clinica

Sponsor organisation

GOIRC Gruppo Oncologico Italiano Di Ricerca Clinica

Address

Viale Antonio Gramsci 14

City

Parma

Postcode

43126

Country

Italy

Scientific contact point

Organisation

GOIRC Gruppo Oncologico Italiano Di Ricerca Clinica

Contact name

Carmine Pinto

Public contact point

Organisation

GOIRC Gruppo Oncologico Italiano Di Ricerca Clinica

Contact name

Carmine Pinto

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications