AGNOSTIC THERAPY IN A PHASE II SINGLE-ARM STUDY IN FIRST-LINE TREATMENT OF DURVALUMAB IN ASSOCIATION WITH CARBOPLATIN OR CISPLATIN AND ETOPOSIDE IN PATIENTS AFFECTED BY EXTENSIVE STAGE - EXTRAPULMONARY SMALL CELL CARCINOMA

NCT06464068 | Recruiting Phase 2

• 1 other identifier: GOIRC-01-2021
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, single-arm, multicenter study to evaluate the activity and safety of durvalumab in combination with carboplatin or cisplatin plus etoposide in patients with treated ES-EPSCC.

Conditions

Extrapulmonary Small Cell Carcinoma

Keywords

EXTRAPULMONARY SMALL CELL CARCINOMA (EPSCC); DURVALUMAB

Outcome Measures

Primary Outcomes (1)

• progression free survival (PFS)

  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. PFS isdefined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. According to the results of the CASPIAN trial \[18\] in which was observed a 12-month progression-free survival rates of 5% (2.4-8.0) for patients that had received Platinum-etoposide, it is expected to detect an increasing of at least 10 percentage points (to 15%).

  12 months

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  12 months

• Disease control rate (DCR)

  12 months

• Overall survival (OS)

  24 months

• Duration of response (DOR)

  12 months

• quality of life (QoL)

  24 months

Other Outcomes (1)

• biomarkers associated with sensitivity/resistance to immune checkpoint inhibitors

  24 months

Study Arms (1)

DURVALUMAB IN ASSOCIATION WITH CARBOPLATIN OR CISPLATIN AND ETOPOSIDE

EXPERIMENTAL

All drugs will be administered intravenously. Induction treatment will be administered on a 21-day cycle for four cycles and will consist of: * etoposide 80-100 mg/m² (administered on days 1-3 of each 21-day cycle); * investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m² (administered on day 1 of each cycle); * durvalumab 1500 mg every 3 weeks in combination with chemotherapy (induction phase) followed by maintenance phase with durvalumab 1500 mg every 4 weeks. Patients will continue treatment until disease progression per investigator assessment, unacceptable toxicity, or other discontinuation criteria were met for a maximum of 24 months. Continuation of study treatment after disease progression will be permitted if there is evidence of clinical benefit for a maximum 24 months.

Drug: Durvalumab

Interventions

Durvalumab DRUG

All drugs will be administered intravenously. Induction treatment will be administered on a 21-day cycle for four cycles and will consist of: * etoposide 80-100 mg/m² (administered on days 1-3 of each 21-day cycle); * investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m² (administered on day 1 of each cycle); * durvalumab 1500 mg every 3 weeks in combination with chemotherapy (induction phase) followed by maintenance phase with durvalumab 1500 mg every 4 weeks. Patients will continue treatment until disease progression per investigator assessment, unacceptable toxicity, or other discontinuation criteria were met for a maximum of 24 months. Continuation of study treatment after disease progression will be permitted if there is evidence of clinical benefit for a maximum 24 months.

Also known as: Etoposide, Cisplatin. Carboplatin

DURVALUMAB IN ASSOCIATION WITH CARBOPLATIN OR CISPLATIN AND ETOPOSIDE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. Histologically or cytologically confirmed extensive disease extrapulmonary small cell carcinoma.
• \. 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:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.0 × 109 /L
• Platelet count ≥75 × 109/L
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). \<\<This will not apply to patients 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 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

You may not qualify if:

• 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
• 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.
• 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.
• 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.
• 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

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead

Study Sites (1)

AUSL-IRCCS of Reggio Emilia

Reggio Emilia, 42123, Italy

RECRUITING

Related Publications (1)

• Damato A, Maglietta G, Antonuzzo L, Berardi R, Buonadonna A, Brighi N, Cinieri S, Di Micco C, Gelsomino F, Grossi F, Martinelli E, Cesario S, Pusceddu S, Spada F, Iachetta F, Gervasi E, Ciardiello G, Normanno N, Pinto C. Agnostic phase II, multicenter, single-arm study with DURVAlumab plus carboplatin or cisplatin and etoposide as first-line treatment in extensive stage - Extrapulmonary Small Cell Carcinoma (EPSCC) patients - DURVASCC trial (GOIRC-01-2021). BMC Cancer. 2025 Nov 12;25(1):1763. doi: 10.1186/s12885-025-15112-w.

  PMID: 41225446 DERIVED

MeSH Terms

Interventions

durvalumab; Etoposide

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Angela Damato, MD

  AUSL/IRCCS of Reggio Emilia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carmine Pinto, MD

CONTACT

+39 0522296614; carmine.pinto@ausl.re.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: June 18, 2024
• Study Start: January 16, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: June 18, 2024

Record last verified: 2024-06

Locations

IT (1)