Clinical trial NCT06419179: Maintenance Durvalumab (MEDI4736) and Olaparib (AZD2281) After Standard 1st Line Treatment (Carboplatin/Cisplatin, Etoposide, Durvalumab) in HRD Positive Extensive Disease (ED) Small-cell Lung Cancer (SCLC)
Official title: A Multicenter Phase II Trial of Maintenance Durvalumab (MEDI4736) and Olaparib (AZD2281) After Standard 1st Line Treatment (Carboplatin/Cisplatin, Etoposide, Durvalumab) in Homologous Recombination Deficiency (HRD) Positive Extensive Disease (ED) Small-cell Lung Cancer (SCLC)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Small Cell Lung Carcinoma
Lead sponsor: University of Cologne
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2024-05-17
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Maintenance durvalumab (MEDI4736) and olaparib (AZD2281) after standard 1st line treatment (carboplatin/ cisplatin, etoposide, durvalumab) in HRD positive extensive disease (ED) small-cell lung cancer (SCLC)


Eligibility criteria: Inclusion Criteria Pre-Screening:

* Newly diagnosed, histologically documented advanced or metastatic small-cell lung cancer (UICC stage III which is not amenable to curative radiochemotherapy or stage IV). \[...\]
* Either de novo biopsies collected as part of routine clinical practice or archival tumor samples (taken ≤6 months prior to screening) are acceptable.
* Planned or ongoing treatment with carboplatin/cisplatin, etoposide, durvalumab as 1st-line SoC. Pre-screening must begin no later than the start of the 3rd cycle to allow sufficient time for molecular analyses. \[...\]
* Available radiographic chest and abdominal CT or MRI scans performed up to 42 days before initial first line treatment with carboplatin/cisplatin, etoposide and durvalumab.
* At least one measurable site of disease as defined by RECIST v1.1 criteria.
* \[...\]

Inclusion Criteria Screening:

* Completed pre-screening with fulfillment of all inclusion and exclusion criteria of pre-screening. Pre-screening must have tested positive for homologous recombination deficiency as defined in this protocol at central testing. \[...\]
* Patients must not have radiographic or clinic disease progression while on induction therapy and/or prior to start of study treatment.
* Patients must have received 4 cycles (21-day cycles) of induction with carboplatin or cisplatin, etoposide and durvalumab completed within 1 to 14 days prior to initiation of study treatment on C5D1. Patients must have received durvalumab at minimum three times during the four induction cycles.
* Adequate organ and marrow function

Exclusion Criteria Pre-Screening:

* Induction therapy other than carboplatin/cisplatin, etoposide and durvalumab. (The administration of one induction cycle without durvalumab is permitted.)
* Radiographic or clinical evidence of progressive disease.
* Negative HRD result in a previous pre-screening in this trial.
* \[...\]

Exclusion Criteria Screening:

* Patients with symptomatic uncontrolled central nervous system (CNS) metastases.
* Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
* History of leptomeningeal carcinomatosis.
* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy. Exceptions are:

  1. Alopecia (any Grade)
  2. Vitiligo (any Grade)
  3. Hypothyroidism stable on hormone replacement (Grade ≤2)
  4. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician
  5. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or olaparib may be included only after consultation with the Sponsor.
  6. ...

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Approximately two years (from First patient in (FSI) to Last patient last visit (LSLV))
Secondary outcomes:
measure: Incidence, severity and grading of adverse events (AE) and seriouse adverse events (SAE).
timeFrame: Approximately two years (from FSI to LSLV)
measure: ORR of maintenance.
timeFrame: Approximately two years (from FSI to LSLV)
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: University Hospital Cologne
state: North Rhine-Westphalia
Study officials:
affiliation: University Hospital Cologne
name: Jürgen Wolf, MD
role: PRINCIPAL_INVESTIGATOR
References: