Neoplasms

All Conditions

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Adenocarcinoma

Adenocarcinoma, Mucinous

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Carcinoma

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Neoplasms by Histologic Type

Neoplasms, Cystic, Mucinous, and Serous

Adenocarcinoma of the Appendix

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Nivolumab

Oxaliplatin

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Immune Checkpoint Inhibitors

Levoleucovorin

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Antineoplastic Agents, Immunological

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

The study has a start-up single-arm design consisting of 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 4 individual cycles before radiologic response assessment and patient stratification to continued therapy or not.

Patients who present less than 10% target lesion reduction at the first radiologic response assessment will proceed to standard-of-care treatment at the Clinical Investigator's discretion.

Patients who present 10% or higher target lesion reduction at the first radiologic response assessment will continue with alternating 2 cycles of the Nordic FLOX regimen and 2 cycles of nivolumab in a go-and-stop schedule until progressive disease on ongoing therapy (defining PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.

Q2W

Nivolumab: 240 mg fixed dose over 30 minutes, IV administration every 2 weeks

Anne H Ree, MD, PhD

Eva Hofsli, MD, PhD

Eva Hoflsi, MD, PhD

Christian Kersten, MD, PhD

Hanne M Hamre, MD, PHD

Jørgen Smeby, MD, PhD

Hypothesis: Patients with metastatic colorectal cancer with DNA mismatch repair-proficient (pMMR) function / microsatellite-stable (MSS) phenotype harbor a non-immunogenic disease that can be transformed into an immunogenic condition by short-course oxaliplatin-based therapy, and may achieve durable disease control or even tumor eradication by the addition of immune checkpoint blockade therapy to the standard-of-care oxaliplatin-based treatment.

The study has a start-up single-arm design consisting of 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 4 individual cycles (8 weeks, or longer if cycles have been delayed) before radiologic response assessment and patient stratification to continued therapy.

Patients who present less than 10% target lesion reduction at the first radiologic response assessment will proceed to standard-of-care treatment at the Clinical Investigator's discretion. Patients will be followed for PFS (from the date of study enrolment).

Patients who present 10% or higher target lesion reduction at the first radiologic response assessment will continue treatment with alternating 2 cycles of the Nordic FLOX regimen and 2 cycles of nivolumab. From the time of stratification, radiologic response assessment will be every 8 weeks. After a total of 12 individual cycles (4 initial cycles followed by 8 continuation cycles; Sequence 1), patients will enter a break that will persist until disease progression, following radiologic assessment every 8 weeks during the break, when therapy is reintroduced and administered for another total of 12 individual cycles (Sequence 2) before a new break. This go-and-stop schedule will be continued until progressive disease on ongoing therapy (defining PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.

METIMMOX-2: Metastatic pMMR/MSS Colorectal Cancer - Shaping Anti-Tumor Immunity by Oxaliplatin

The listed study information can be made available from the Principal Investigator on reasonable request and in accordance with the General Data Protection Regulation of the European Union.

To determine PFS, in terms of continuation of treatment strategy, of repeat sequential treatment with the Nordic FLOX regimen and nivolumab in patients with previously untreated unresectable metastatic pMMR/MSS colorectal cancer reaching 10% or higher target lesion reduction at the first radiologic restaging.

Oslo University Hospital

St. Olavs Hospital

University Hospital, Akershus

Principal Investigator

Spots Global Cancer Trial Database for immune checkpoint inhibitor (nivolumab)