Clinical trial NCT06792695: A Study of Novel Study Interventions and Combinations in Participants With Colorectal Cancer
Official title: A Phase II, Open-label, Multicenter, Master Protocol to Evaluate the Safety and Efficacy of Novel Study Interventions and Combinations in Participants With Colorectal Cancer (CANTOR)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic disease
Immunotherapy
Liver metastasis
Mismatch-repair-proficient
Antibody targeting
Colorectal Cancer
CANTOR
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2025-01-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety and efficacy of novel study interventions and combinations in participants with Colorectal Cancer (CRC).

Detailed description: This is a Phase II, platform, open-label, multi-drug, multicenter, global study.

This is a modular study, that includes a master protocol and substudies.

Partcipants will be randomised to one of the following intervention groups:

* Volrustomig + FOLFIRI + bevacizumab group (Arm A)
* FOLFIRI + bevacizumab group (Arm B)

The substudy will evaluate the effects of volrustomig in combination with FOLFIRI (irinotecan, 5-FU, and leucovorin) and bevacizumab versus FOLFIRI and bevacizumab only in participants with Mismatch-repair-proficient (pMMR)/Microsatellite stable (MSS) metastatic CRC (mCRC) in the absence of liver metastases and who have not received previous systemic treatment for advanced or metastatic disease.

Eligibility criteria: Overall Inclusion Criteria:

* Histopathologically confirmed colorectal adenocarcinoma.
* Provision of FFPE tumor sample collected as per SoC.
* Presence of measurable disease by RECIST 1.1 criteria.
* ECOG performance status of 0 or 1.
* Life expectancy ≥ 12 weeks at the time of screening.

Substudy Inclusion Criteria:

* No radiological evidence of liver metastasis.
* No prior systemic therapy for mCRC, except for neoadjuvant/adjuvant chemotherapy where, \> 6 months have elapsed between completion of therapy and documented date of diagnosis of recurrent or metastatic disease.
* Known pMMR/MSS status (only pMMR/MSS mCRC allowed).
* Adequate organ and bone marrow function
* Body weight \> 35 kg at screening and at randomization.
* Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Overall Exclusion Criteria:

* Central nervous system metastases or spinal cord compression
* Known history of severe allergy to any monoclonal antibody or study intervention.
* Any unresolved toxicity CTCAE Grade ≥ 2 from a previous anticancer therapy.
* History of another primary malignancy.

Substudy Exclusion Criteria:

* Potentially resectable disease with multidisciplinary plan for radical surgery.
* Active or prior documented autoimmune or inflammatory disorders or cardiac conditions.
* Participants with a prior history of hypertensive crisis or hypertensive encephalopathy or bleeding risks.
* Deep venous thrombosis, pulmonary embolism, arterial thrombosis, transient ischemic attack or cerebrovascular accident.
* History of abdominal or tracheoesophageal fistula, GI perforation and/or fistulae, or intraabdominal abscess within 6 months prior to randomization.
* Prior exposure to immune mediated therapy.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Approximately 3 years
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Approximately 3 years
measure: Objective Response Rate (ORR)
timeFrame: Approximately 3 years
measure: Disease Control Rate (DCR)
timeFrame: Approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Approximately 3 years
measure: Time to second progression or death (PFS2)
timeFrame: Approximately 3 years
measure: Maximum Observed Concentration (Cmax)
timeFrame: Approximately 3 years
measure: Observed lowest concentration before the next dose is administered (Ctrough)
timeFrame: Approximately 3 years
measure: Number of patients with positive Antidrug Antibodies (ADAs)
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Rochester
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
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state: Oregon
city: Philadelphia
country: United States
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state: Pennsylvania
city: Nashville
country: United States
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state: Tennessee
city: Houston
country: United States
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state: Texas
city: East Melbourne
country: Australia
facility: Research Site
city: Wollongong
country: Australia
facility: Research Site
city: Woodville South
country: Australia
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city: Victoria
country: Canada
facility: Research Site
state: British Columbia
city: Barrie
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Zhengzhou City
country: China
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Marseille Cedex 9
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Saint-Priez En Jarez
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Castelfranco Veneto
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Yongin-si
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Zwolle
country: Netherlands
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: València
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Yung Kang City
country: Taiwan
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
References: