## Protocol Section
### Identification Module
**NCT ID:** NCT06419179

**Acronym:** GUIDANCE

**Brief Title:** 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)

#### Organization Study ID Info
**ID:** Uni-Koeln-5159
#### Organization
**Class:** OTHER
**Full Name:** University of Cologne
#### Secondary ID Infos
**ID:** 2024-512373-27-00
**Type:** CTIS
### Status Module
#### Completion Date
**Date:** 2026-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-03
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** AstraZeneca

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Cologne

#### Responsible Party

**Investigator Affiliation:** University of Cologne

**Investigator Full Name:** Prof. Dr. Juergen Wolf

**Investigator Title:** Clinical Prof. Dr. Jürgen Wolf

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** True

**Oversight Has DMC:** True

### Description Module

**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)

### Conditions Module

**Conditions:**

- Small Cell Lung Carcinoma

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 29

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Study treatment (olaparib and durvalumab) starts with the initiation of maintenance therapy and is administered at a 28-day cycle until progression, unacceptable toxicity, or discontinuation for other reasons.

Induction therapy (four cycles of carboplatin/cisplatin, etoposide, durvalumab) is administered as part of standard of care.

**Intervention Names:**

- Drug: Durvalumab

- Drug: Olaparib

**Label:** Combination of olaparib and durvalumab after four cycles of standard 1st line treatment

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Combination of olaparib and durvalumab after four cycles of standard 1st line treatment

**Description:** 1500 mg i.v. Q4W

**Name:** Durvalumab

**Other Names:**

- MEDI4736

- IMFINZI

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Combination of olaparib and durvalumab after four cycles of standard 1st line treatment

**Description:** 300 mg BID orally

**Name:** Olaparib

**Other Names:**

- AZD2281

- LYNPARZA

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** PFS according to investigator-assessed RECIST 1.1 from start of maintenance therapy

**Measure:** Progression-free survival (PFS)

**Time Frame:** Approximately two years (from First patient in (FSI) to Last patient last visit (LSLV))

#### Secondary Outcomes

**Description:** Grading is based on CTCAE Version 5

**Measure:** Incidence, severity and grading of adverse events (AE) and seriouse adverse events (SAE).

**Time Frame:** Approximately two years (from FSI to LSLV)

**Description:** Grading is based on RECIST 1.1

**Measure:** ORR of maintenance.

**Time Frame:** Approximately two years (from FSI to LSLV)

### Eligibility Module

**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 chemoimmunotherapy with carboplatin or cisplatin, etoposide and durvalumab completed within 1 to 14 days prior to initiation of study treatment on C5D1.
* Adequate organ and marrow function

Exclusion Criteria Pre-Screening:

* Induction therapy other than carboplatin/cisplatin, etoposide and durvalumab.
* 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. ...

**Maximum Age:** 120 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** juergen.wolf@uk-koeln.de

**Name:** Jürgen Wolf, MD

**Phone:** +49 221 478

**Phone Ext:** 89050

**Role:** CONTACT

**Contact 2:**

**Email:** felix.john@uk-koeln.de

**Name:** Felix John, MD

**Role:** CONTACT

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

- ID: D000008175

- Term: Lung Neoplasms

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M11172

- Name: Lung Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M28323

- Name: Small Cell Lung Carcinoma

- Relevance: HIGH

- As Found: Small Cell Lung Carcinoma

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T5271

- Name: Small Cell Lung Cancer

- Relevance: HIGH

- As Found: Small Cell Lung Cancer

### Condition Browse Module - Meshes

- ID: D000055752

- Term: Small Cell Lung Carcinoma

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000067856

- Term: Poly(ADP-ribose) Polymerase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6182

- Name: Cisplatin

- Relevance: LOW

- As Found: Unknown

- ID: M18650

- Name: Carboplatin

- Relevance: LOW

- As Found: Unknown

- ID: M272500

- Name: Durvalumab

- Relevance: HIGH

- As Found: Non-Small Cell

- ID: M233003

- Name: Olaparib

- Relevance: HIGH

- As Found: Fentanyl

- ID: M8191

- Name: Etoposide

- Relevance: LOW

- As Found: Unknown

- ID: M341643

- Name: Etoposide phosphate

- Relevance: LOW

- As Found: Unknown

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

- ID: M205

- Name: Poly(ADP-ribose) Polymerase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000613593

- Term: Durvalumab

- ID: C000531550

- Term: Olaparib

### Misc Info Module

- Version Holder: 2024-05-24
