Sonntag, 13. Juni 2021
Navigation öffnen
Anzeige:
CAR T Prelaunch
CAR T Prelaunch
 
JOURNAL ONKOLOGIE – STUDIE

Thoracic Radiotherapy Plus Maintenance Durvalumab After First Line Carboplatin and Etoposide Plus Durvalumab in Extensive-stage Disease Small Cell Lung Cancer (ED-SCLC).

Noch nicht rekrutierend

NCT-Nummer:
NCT04472949

Studienbeginn:
Mai 2021

Letztes Update:
01.03.2021

Wirkstoff:
Durvalumab, Carboplatin, Etoposide

Indikation (Clinical Trials):
Lung Neoplasms, Small Cell Lung Carcinoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Swiss Group for Clinical Cancer Research

Collaborator:
-

Studienleiter

Alfredo Addeo, Prof
Study Chair
Hôpitaux Universitaires Genève

Kontakt

Studienlocations
(3 von 14)

IOSI Ospedale Regionale di Bellinzona e Valli
6500 Bellinzona
Switzerland» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

The prognosis of patients with advanced small cell lung cancer is poor. Despite chemotherapy

and immunotherapy, median survival is only 12 months. The trial SAKK 15/19 is investigating

whether thoracic radiotherapy and the administration of durvalumab can slow down the

progression of the disease.

In patients with advanced small cell lung cancer, the standard therapy consists of 4-6 cycles

of platinum-based chemotherapy plus etoposide with or without Atezolizumab. Nevertheless, the

median overall survival of these patients is only 10-12 months, because resistance to the

therapy usually develops rapidly.

Radiotherapy and maintenance therapy with Durvalumab to activate the immune system The risk

of intrathoracic progression of small cell lung cancer can be reduced by additional thoracic

radiotherapy. It is assumed that the radiation not only has a direct cytotoxic effect on the

tumor cells, but also stimulates an antitumor immune response.

In the trial SAKK 15/19, it is being investigated whether the combination of the monoclonal

anti-PD-L1 antibody durvalumab with thoracic radiotherapy in patients with advanced small

cell lung cancer can cause an even stronger activation of the immune system with an improved

antitumoral immune response. The trial therapy (thoracic radiotherapy + durvalumab) is based

on chemo-immunotherapy with carboplatin, etoposide and durvalumab. The primary endpoint of

the trial is the progression-free rate after 12 months, secondary endpoints include

progression-free survival, median overall survival and objective response rate.

Which patients can participate? The trial is open to patients with advanced small-cell lung

cancer who have either metastases (stage IV) or whose lung tumor volume is so large that

radiation therapy with curative intent is not possible as a first-line therapy (stage

III-IV). Patients who have already received systemic therapy or thoracic radiotherapy because

of the small cell lung carcinoma cannot participate.

Conduct of the trial

Participation in the trial is carried out in three phases for patients:

- Induction therapy: Patients receive four cycles of chemo-immunotherapy with carboplatin,

etoposide and durvalumab. One cycle lasts 21 days. In those patients who show a response

or stable disease situation after completion of induction therapy, maintenance therapy

follows. Maintenance therapy is not performed in patients whose disease has progressed

further under induction therapy.

- Maintenance therapy: Thoracic radiotherapy for 2.5-3 weeks (13 fractions of 3 Gray each)

and administration of Durvalumab every 28 days for a maximum of two years.

- Follow-up for two years.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Written informed consent according to Swiss law and ICH-GCP E6(R2) regulations before

registration and prior to any trial specific procedures

- Histologically or cytologically1 confirmed extensive disease stage IV SCLC (T any, N

any, M1 a/b) or T3-4 due to multiple lung nodules that are too extensive or have

tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan

(according to American Joint Committee on Cancer Stage (8th edition)

- Patients must be considered suitable to receive carboplatin with etoposide as 1st line

treatment for the ED-SCLC

- Patients with brain metastases are also eligible provided they are asymptomatic or

treated central nervous system metastases and meet the following criteria:

- No ongoing requirement for corticosteroids at least 2 weeks prior to trial

treatment

- No leptomeningeal disease

- Patients with a prior malignancy other than SCLC and treated with curative intention

are eligible, if all treatment of that malignancy was completed at least 2 years

before registration and the patient has no evidence of disease at registration. Less

than 2 years is acceptable for malignancies with low risk of recurrence and/or no late

recurrence, after consultation with the Coordinating Investigator

- Measurable disease per RECIST v1.1

- Age ≥ 18 years

- WHO performance status 0-1

- Adequate pulmonary function: forced expiratory volume in one second FEV (1) ≥ 1.0

liter

- Adequate bone marrow function:

- Absolute neutrophil count ≥ 1.5 x 109/L1

- Platelet count ≥ 100 x 109/L

- Hemoglobin ≥ 90 g/L

- Adequate hepatic function:

- Total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x

ULN)

- AST and/or ALT ≤ 2.5 x ULN (in patients with hepatic metastasis: AST and/or ALT ≤

5.0 x ULN)

- Adequate renal function measured (by the CKD-EPI formula) or calculated creatinine

clearance ≥ 45 mL/min (by the Cockcroft-Gault formula)

- Women of childbearing potential must use highly effective contraception, are not

pregnant or lactating and agree not to become pregnant during trial treatment and

until 90 days after the last dose of investigational drug. A negative serum pregnancy

test performed within 7 days before registration is required for all women of

childbearing potential

- Men agree not to donate sperm or to father a child during trial treatment and until 90

days after the last dose of investigational drug

Exclusion criteria:

- Spinal cord compression not definitively treated with surgery and/or radiation or

previously diagnosed and treated spinal cord compression without evidence that disease

has been clinically stable for ≥ 1 week prior to registration

- Prior chemotherapy treatment for ED-SCLC

- Any history of radiotherapy to the chest. Radiation therapy outside of the chest for

palliative care (i.e., bone metastasis) is allowed but must be completed before first

dose of -

- Prior systemic treatment including immune checkpoint inhibitors against SCLC

- Concomitant treatment within 30 days of registration with any other experimental drug

and/or enrollment in another clinical trial

- Concomitant use of other anti-cancer drugs or radiotherapy. Except surgery for local

pain control

- Severe or uncontrolled cardiovascular disease

- Congestive heart failure NYHA III or IV;

- Unstable angina pectoris

- History of myocardial infarction within the last 3 months

- Serious arrhythmias requiring medication (with exception of atrial fibrillation

or paroxysmal supraventricular tachycardia)

- Uncontrolled hypertension

- Uncontrolled or symptomatic hypercalcemia, i.e.

- > 1.5 mmol/L ionized calcium

- > 12 mg/dL or > 3 mmol/L corrected serum calcium

- Known interstitial lung disease

- Body weight ≤ 30 kg

- Major surgical procedure (defined by the investigator) within 28 days prior to the

first dose of durvalumab or anticipation of need for a major surgical procedure during

the course of the trial

- Known history of active primary immunodeficiency

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or

Hepatitis B Virus infection or any uncontrolled active systemic infection requiring

intravenous antimicrobial treatment

- Known history of allogeneic organ transplantation

- Active or prior documented autoimmune or inflammatory disorders including:

- Inflammatory bowel disease (e.g., colitis or Crohn's disease)

- Systemic lupus erythematosus

- Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid

arthritis, hypophysitis, uveitis, etc.)

- Patients with eczema, psoriasis, lichen simplex chronicus are not permitted, except

they are with dermatologic manifestations only (e.g., patients with psoriatic

arthritis would be excluded) and meet the following conditions:

- Rash must cover less than 10% of body surface area

- Disease is well controlled at baseline and only requires low potency topical

steroids

- No acute exacerbations of underlying condition within the last 12 months (not

requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids,

biologic agents, oral calcineurin inhibitors, high potency, or oral steroids)

- Patients with a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic

treatment (systemic steroids or immunosuppressive agents) or has a clinical

symptomatology suggesting worsening of PNS

- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis

obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active

pneumonitis on screening thorax CT scan

- Receipt of live attenuated vaccine within 30 days prior to the first dose of

durvalumab

- Concomitant or prior use, i.e. within 14 days before the first dose of durvalumab, of

immunosuppressive medication including immunosuppressant, such as methotrexate,

azathioprine and tumor necrosis factor (TNF)-α blockers, with the exceptions of:

- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra

articular injection)

- Systemic corticosteroids at physiological doses not to exceed 10 mg/day of

prednisone or an equivalent corticosteroid

- Steroids as premedication for hypersensitivity reactions (e.g., CT scan

premedication) and premedication for chemotherapy

- Known hypersensitivity to the drugs used in this trial (carboplatin, etoposide,

durvalumab)

- Any other serious underlying medical, psychiatric, psychological, familial or

geographical condition, which in the judgment of the investigator may interfere with

the planned staging, treatment and follow-up, affect patient compliance or place the

patient at high risk from treatment-related complications.

Studien-Rationale

Primary outcome:

1. Progression-free rate (PFR) (RECIST v.1.1) (Time Frame - at 12 months after registration):
PFR (RECIST v.1.1) at 12 months after registration, defined by the Kaplan-Meier estimator for progression-free survival (RECIST v.1.1) at 12 months (+ 4 weeks as we allow 4 weeks delay in the tumor assessment at 12 months).



Secondary outcome:

1. Progression-free survival (PFS) (RECIST v.1.1) (Time Frame - From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration.):
PFS (RECIST v.1.1), defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first. Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment before the start of the new therapy, if any.

2. Progression-free survival (PFS) (RECIST v.1.1) outside the brain (Time Frame - From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration):
PFS (RECIST v.1.1) outside the brain, defined as progression-free survival, except that relapses in the brain will be censored.

3. Progression-free survival (RECIST v.1.1) after induction chemotherapy (PFS-IND) (Time Frame - From the date of completion of induction chemotherapy until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration):
PFS-IND defined as the time from completion of induction chemotherapy until progression according to RECIST v1.1 or death from any cause, whichever occurs first. Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment before the start of the new therapy, if any. PFS-IND will only be analyzed in patients who had CR, PR or SD after induction chemotherapy and started radiotherapy maintenance.

4. Overall Survival (OS) (Time Frame - From the date of registration until the date of death, assessed up to 4 years after registration):
OS defined as the time from registration until death from any cause. Patients without an event at the time of analysis will be censored at the date they were last known to be alive.

5. Objective response rate (ORR) (Time Frame - From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration):
ORR defined as proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 during trial treatment.

6. Duration of response (DOR) (Time Frame - From the date of first CR or PR according to RECIST v1.1 until the date of progressive disease according to RECIST v1.1, relapse or death, whichever occurs first, assessed up to 4 years after registration):
DOR defined as time from the date when a patient first meets the criteria for CR or PR according to RECIST v1.1, until documented progression, relapse or death due to disease progression, whichever occurs first. Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment before the start of the new therapy, if any. DOR will only be analyzed in patients achieving CR or PR during trial treatment.

7. Adverse events (AEs) (Time Frame - From the date of registration to 90 days after last trial treatment):
AEs assessed according to NCI CTCAE 5.0.

Geprüfte Regime

  • Durvalumab (MEDI4736):
    Durvalumab: 1500 mg iv
  • carboplatin:
    Carboplatin: AUC 5 mg/mL/min iv
  • etoposide:
    Etoposide: 100 mg/m2 iv
  • Thoracic radiotherapy:
    Thoracic radiotherapy: 39 Gy in 13 fractions, starting 3-8 weeks after day 1 of last cycle of induction treatment, over 2.5 weeks Prophylactic cranial irradiation (PCI) is allowed but optional: according to local practice, starting 3-8 weeks after day 1 of last cycle of induction treatment Follow up phase Patients will be followed up for 24 months, every 8 weeks.

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren