## Protocol Section
### Identification Module
**NCT ID:** NCT03149679

**Brief Title:** The p53 Colorectal Cancer Trial

**Official Title:** Treatment of Patients With Metastatic Colorectal Cancer Harboring TP53 Mutations With Dose-dense Cyclophosphamide - the p53 Colorectal Cancer Trial

#### Organization Study ID Info
**ID:** 2016/1637
#### Organization
**Class:** OTHER
**Full Name:** Haukeland University Hospital
### Status Module
#### Completion Date
**Date:** 2020-08-07

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-01-22

**Type:** ACTUAL

**Last Update Submit Date:** 2021-01-20

**Overall Status:** TERMINATED

#### Primary Completion Date
**Date:** 2020-08-07

**Type:** ACTUAL

#### Start Date
**Date:** 2017-05-09

**Type:** ACTUAL

**Status Verified Date:** 2020-02

#### Study First Post Date
**Date:** 2017-05-11
**Type:** ACTUAL
**Study First Submit Date:** 2017-03-14
**Study First Submit QC Date:** 2017-05-09
**Why Stopped:** The study was discontinued after the first pre-planned interim analysis due to insufficient response rates.
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Haukeland University Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Single center, open labeled, phase 2 clinical trial, where patients with metastatic colorectal cancer are selected for treatment with dose dense Cyclophosphamide every second week based on TP53 mutation status; i.e. only patients with TP53 mutated tumors may be included in the treatment arm.

### Conditions Module

**Conditions:**

- Colorectal Cancer Metastatic

- Colorectal Cancer Stage IV

- TP53 Gene Mutation

**Keywords:**

- Cyclophosphamide

- Colorectal Cancer Metastatic

- TP53 Gene Mutation

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Single center, open labeled, phase 2 clinical trial, where patients are selected for treatment based on upfront TP53 mutation status; i.e. only patients with TP53 mutated tumors may be included in the single treatment arm. The informed consent, however needs to be signed prior to a biopsy for TP53 mutation analyses; thus, all patients are formally enrolled in the study prior to tissue collection, and the full population tested will be accounted for despite the fact that only patients with TP53 mutated tumors may enter the single treatment arm.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 12

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week.

**Intervention Names:**

- Drug: Cyclophosphamide

**Label:** Cyclophosphamide arm

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cyclophosphamide arm

**Description:** Chemotherapy

**Name:** Cyclophosphamide

**Other Names:**

- Sendoxan

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Partial response (PR) or complete response (CR) as defined by the RECIST criteria

**Measure:** Objective response rate (ORR)

**Time Frame:** 4 months

#### Secondary Outcomes

**Description:** Tissue and blood sampling at baseline and whenever treatment is changed

**Measure:** Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined.

**Time Frame:** 10 years

**Description:** Tissue and blood sampling at baseline and whenever treatment is changed

**Measure:** Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups

**Time Frame:** 10 years

**Description:** Stable disease (SD) \>6 months, PR or CR

**Measure:** Clinical benefit rate (CBR)

**Time Frame:** 5 years

**Description:** Survival analyses

**Measure:** Recurrence-free and overall survival, compared to historical data

**Time Frame:** All patients will be followed for 5 years or until death to record survival outcome

**Description:** Clinical examination and blood samples

**Measure:** Safety and tolerability of the study treatment including recording of number of participants with treatment-related adverse events as assessed by CTCAE v4.0

**Time Frame:** Every second week during the treatment period from start of treatment, and thereafter every second month for 5 years or until death

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Metastatic colorectal cancer patients for whom conventional therapy has failed; defined as 2 lines of chemotherapy including oxaliplatin or irinotecan- containing regimens as well as an EGFR inhibitor if applicable.
* Tumor lesion suitable for biopsy
* Age \>18 years
* Clinically or radiologically measurable tumor deposits according to the RECIST criteria
* WHO performance status 0-1
* Radiology studies (CT thorax/abdomen/pelvis) and echo cor and ECG must be performed within 28 days prior to registration.
* Before patient registration in the trial, written informed consent must be given according to national and local regulations.
* Blood test requirements:

Neutrophils \> 1.0 e9/L Platelets \> 75 e9/L Bilirubin \< 20 µmol / L. Serum creatinine \< 1.5 x ULN

Exclusion Criteria:

* Co-morbidity including, but not limited to, impaired renal-, liver or bone marrow function, that based on the assessment of the treating physician, may preclude the use of cyclophosphamide at actual doses.
* Known hypersensitivity to the study drug, its metabolites or any excipients in the infusion solution.
* Psychological, familial, sociological or geographical condition(s) potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
* Pregnant or lactating patients cannot be included.
* Clinical evidence of serious coagulopathy. Prior arterial/venous thrombosis or embolism does not exclude patients from inclusion, unless patient is considered unfit by study oncologist.
* Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Bergen

**Country:** Norway

**Facility:** Haukeland University Hospital

**Zip:** 5021

#### Overall Officials

**Official 1:**

**Affiliation:** Haukeland University Hospital

**Name:** Inger Marie Løes, MD PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007414

- Term: Intestinal Neoplasms

- ID: D000005770

- Term: Gastrointestinal Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000003108

- Term: Colonic Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000012002

- Term: Rectal Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M17890

- Name: Colorectal Neoplasms

- Relevance: HIGH

- As Found: Colorectal Cancer

- ID: M10448

- Name: Intestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6336

- Name: Colonic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14844

- Name: Rectal Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000015179

- Term: Colorectal Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000000477

- Term: Alkylating Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000019653

- Term: Myeloablative Agonists

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6727

- Name: Cyclophosphamide

- Relevance: HIGH

- As Found: Cycle

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000003520

- Term: Cyclophosphamide

### Misc Info Module

- Version Holder: 2024-05-24
