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Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN)

ConditionsColorectal CancerResectable Colorectal Carcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGruppo Oncologico del Nord-Ovest

About this trial

This is a window-of-opportunity umbrella platform trial enrolling non-metastatic resectable colorectal patients selected for the presence of a specific targetable molecular alteration. The study aims to test the activity of specific targeted agents/combinations given as a short-course pre-operative strategy, matched with the specific alteration detected, followed by standard of care surgery.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Provide a signed and dated informed consent document.

Age ≥ 18 years at time of informed consent.

ECOG PS of 0 and 1.

Histologically confirmed colorectal cancer adenocarcinoma that is judged as initially resectable with elective surgery aimed at radical intent with R0 margins as per multidisciplinary team assessment.

Disqualifiers

Distant metastases at any site, as defined by negativity of chest/abdomen/pelvis contrast-enhanced computed tomography (CT).

Risk criteria for obstructing disease at radiology or endoscopy as defined in the pivotal FOxTROT study.

Need to receive neoadjuvant radiation or chemoradiation in patients with rectal cancer.

Patients with known hypersensitivity to the study drug of the assigned cohort or to its excipients or to drugs belonging to the same drug class.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Trastuzumab deruxtecan

    Drug

    trastuzumab deruxtecan 5.4 mg/kg IV on day 1

  • Durvalumab

    Drug

    durvalumab 1500 mg IV on day 1

  • Panitumumab

    Drug

    panitumumab 6 mg/kg IV on days 1 and 15

  • Botensilimab

    Drug

    botensilimab 1 mg/kg on day 1

  • Balstilimab

    Drug

    balstilimab 3 mg/Kg on days 1 and 15

  • Sotorasib

    Drug

    sotorasib 960 mg orally once daily from day 1 to 28

  • Vorbipiprant

    Drug

    vorbipiprant 90 mg orally bid from day 1 to 28

  • Nivolumab

    Drug

    240 mg IV on days 1 and 15

  • Amivantamab

    Drug

    amivantamab at the dose of 1600 mg (2240 mg if body weight ≥ 80 Kg), subcutaneously, on days 1, 8, 15 and 22

  • Botensilimab

    Drug

    Botensilimab at the dose of 75 mg, IV on day 1

  • Balstilimab

    Drug

    balstilimab at the dose of 240 mg, IV on days 1, 15, 29 and 43

Treatment groups

197 Participants
are divided into 13 treatment groups

13

Treatment groups

See each treatment group below.

Group A: Cohort 1: HER2 positiveExperimental treatment 1 intervention
Group B: Cohort 2: POLE/D1 mutated with ultra-mutated status (>100 Mut/Megabase)Experimental treatment 1 intervention
Group C: Cohort 3: EGFR-dependentExperimental treatment 1 intervention
Group D: Cohort 4: pMMR/MSS statusExperimental treatment 1 intervention
Group E: Cohort 5: pMMR/MSS statusExperimental treatment 2 interventions
Group F: Cohort 6: dMMR/MSI-H statusExperimental treatment 1 intervention
Group G: Cohort 7: dMMR/MSI-H statusExperimental treatment 2 interventions
Group H: Cohort 8: KRAS G12C mutatedExperimental treatment 2 interventions
Group I: Cohort 9: pMMR/MSS statusExperimental treatment 1 intervention
Group J: Cohort 10: pMMR/MSS statusExperimental treatment 2 interventions
Group K: Cohort 11: Left-sided hyperselected regardless of METExperimental treatment 1 intervention
Group L: Cohort 12: Right-sided hyperselected regardless of METExperimental treatment 1 intervention
Group M: UNICORN part II (NEO-UNICORN) - Cohort 1Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

major pathological response rate

percentage of patients, relative to the total of enrolled subjects in the intention-to-treat population for each cohort, who will achieve a pathological complete response (pCR), defined as 0 or less residual viable tumor in both the primary tumor bed and lymphnodes, or major response (pMR), defined as 10% or less residual viable tumor, as per central pathological review in each Cohort.

Time frame
5 weeks

Secondary outcomes

1

Treatment safety

incidence of AE (including SAEs) in each cohort during the short-course pre-operative treatment, assessed according to National Cancer Institute Common Toxicity Criteria version 5.0 (NCI-CTCAE v5.0).

Time frame
5 weeks
2

Overall Toxicity Rate

percentage of patients, relative to the total of enrolled subjects of each cohort, experiencing any grade AE, according to NCI-CTCAE v5.0, during the short-course pre-operative treatment

Time frame
5 weeks
3

G3/4 Toxicity Rate

percentage of patients, relative to the total of enrolled subjects in each cohort, experiencing any specific adverse event of grade 3/4, according to NCI-CTCAE v5.0, during the short-course pre-operative treatment.

Time frame
5 weeks
4

Surgical mortality

the incidence of death occurring within 30 days after surgery in each cohort

Time frame
10 weeks

Other outcomes

1

Disease-free survival

time from enrollment to the first documentation of disease recurrence or death due to any cause, whichever occurs first. DFS will be censored on the date of the last follow-up visit documenting absence of disease for patients who are alive, on study and disease free at the time of the analysis.

Time frame
36 months
2

Overall survival

Overall survival will be defined as the time from enrollment to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.

Time frame
36 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Gruppo Oncologico del Nord-Ovest

Lead sponsor

Source ClinicalTrials.gov
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