Neoplasms

All Conditions

Immune System Diseases

Digestive System Diseases

Carcinoma

Hypersensitivity

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Herbal and Botanical

Immunomodulating Agents

Nivolumab

Ipilimumab

Relatlimab

Celecoxib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Cola

drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)

drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV) drug: celecoxib 200 mg daily (oral)

drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)

drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15

drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29

Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery

Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery

celecoxib will be administered starting day 1 until 1 day before surgery daily (if patient is randomized to group 2 (only applicable for patients with a MSS tumor)

Celecoxib 200mg

BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)

BMS-986253

Relatlimab will be administered IV, in cohort 5 240mg on day 1 and day 15, in cohort 6 480mg on day 1 and day 29

BMS-986016

Marieke van de Belt

A van Lent

T Aukema

P Burger

S Oosterling

E. Hendriks

Myriam Chalabi, MD

In this exploratory study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy + novel IO combinations (i.e. anti-IL 8, COX2-inhibitors). This treatment will be given during the window period until surgical resection of the tumor. The duration of treatment will be approximately 6 weeks.

In this multi-center, open-label, exploratory study, the investigators will enroll 60 patients within two years, including 30 patients with MSS tumors and 30 patients with MSI tumors. Patients with MSS tumors will be randomized to either group 1 or 2. Patients with MSI tumors will all be allocated to group 1.

Patients in group 1 will be treated with a single dose of ipilimumab 1mg/kg on day 1 and two cycles of nivolumab 3mg/kg on day 1 and 15, respectively.

Patients in group 2 will be treated with a single dose of ipilimumab 1mg/kg on day 1, two cycles of nivolumab 3mg/kg one day 1 and 15 and celecoxib daily until the day before surgery.

The study was amended in May 2020 to enroll an additional 70 patients in the MSI cohort after the first 30 patients, making a total of 100 patients with MSI tumors. A formal sample size calculation and primary endpoint of 3-year disease-free-survival (DFS) for this group was added.

The study was amended in July 2021 to add a new cohort, cohort 4, for patients with pMMR/MSS tumors. Once accrual of 30 evaluable patients in group 2 was completed, a new cohort opened in which patients will receive nivolumab plus anti-IL8 (BMS-986253).

The study was amended in November 2022 to add cohort 5 and 6, both in which patients will receive nivolumab plus relatlimab (anti-LAG3). Patients with pMMR/MSS tumors will be randomized 1:1 between cohort 4 and cohort 5, patients with dMMR/MSI tumors will be enrolled in cohort 6.

Accrual for cohort 4 was reached in July 2023. In April 2024, accrual for cohort 6 was reached. Per April 2024 only cohort 5 is open for recruitment.

Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer

Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (Amended Protocol of: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity: The NICHE TRIAL)

Adverse events will be assessed (according to CTCAE v4.0) during treatment and follow-up.

To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival

identify underlying potential escape mechanisms by comparing pre-treatment and post-treatment biopsies

Bristol-Myers Squibb

The Netherlands Cancer Institute

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Substance Related Disorders

Syndrome

Hand-Foot Syndrome

Rectal Diseases

Exanthema

Drug Eruptions

Dermatitis

Skin Diseases

Drug Hypersensitivity

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Capecitabine

Antimetabolites

This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks) in addition to 200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle. The study duration will be the duration of the 6 cycles.

This arm will include 22 patients who will receive 6 cycles of capecitabine-based chemotherapy (cycle is every 3 weeks).

200 mg of oral celecoxib twice daily for 14 days of the 3-week cycle.

Capecitabine-based chemotherapy

Ahmed Mohamed Kettana

Tarek Mohamed Mostafa, Professor of clinical pharmacy

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of malignancy-related mortality. Capecitabine has been approved for the treatment of colorectal cancer as first-line therapy. About 50%-68% of patients who take capecitabine develop Hand-foot syndrome. Hand-foot syndrome (HFS) is the most common adverse event of capecitabine-based chemotherapy. Initial symptoms of HFS are dysesthesia, tingling in the palms, fingers, and soles of the feet, and erythema, which may progress to an extremely painful and debilitating condition without prompt management. These symptoms can potentially lead to a worsened quality of life in patients taking capecitabine-based chemotherapy. Moreover, the adverse reaction necessitates dose-reduction or withdrawal of the chemotherapeutic agent. The mechanisms of HFS are still unknown, and there are limited data available on how to prevent them or manage them. However, different hypotheses of capecitabine-induced HFS pathogenesis have been suggested. One of the hypotheses stated that HFS is a kind of inflammation mediated by cyclooxygenase's (COX-2) over expression in palm and feet by capecitabine and its metabolites causing elevation of inflammatory markers as tumor necrosis factor alpha (TNF-α). COX-2 enzyme plays a main role in inflammation and pain. Therefore, celecoxib which is selective (COX-2) inhibitor may have a key role in the HFS treatment plan. A retrospective study and two prospective studies showed that combining capecitabine with celecoxib, a selective COX-2 inhibitor, can significantly reduce capecitabine-related HFS in colorectal cancer patients. Those studies were dependent on HFS grading only without measuring any markers. So, in our study we assess possible protective effect of celecoxib against capecitabine induced HFS and measure inflammatory marker as tumor necrosis factor alpha (TNF-α), oxidative stress marker as Malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) enzyme to show whether capecitabine induced HFS is caused by COX-2 mediated inflammation or not.

Possible Protective Effect of Celecoxib Against Capecitabine Induced Hand and Foot Syndrome in Patients With Colorectal Cancer

The change in hand and foot syndrome (HFS) grading according to common terminology criteria of adverse events (CTCAE) version 5.0.

Assessment of patients' quality of life using HFS-specific QOL questionnaire (HFS-14) based on patients' symptoms.

The change in serum levels of cyclooxygenase-2 (COX-2) enzyme.

The change in serum levels of tumor necrosis factor alpha (TNF-α) as a inflammatory marker.

The change in serum levels of malondialdehyde (MDA) as oxidative stress marker.

Tanta University

clinical pharmacist

Keratosis, Actinic

Keratosis

Precancerous Conditions

Patient receiving PDT taking 200mg celecoxib.

Control subject not receiving PDT taking 200mg celecoxib.

Control subject not receiving PDT taking placebo.

14 Celecoxib 200mg taken 1 in the morning and 1 in the evening.

14 placebo capsules taken 1 in the morning and 1 in the evening.

Placebo

Jeffrey B Travers, MD, PhD

This study is designed as a double-blinded proof of concept of feasibility study to define if the immunosuppression associated with photodynamic therapy (PDT) can be blocked by treatment with cyclo-oxygenase-2 (COX-2) inhibitor celecoxib in comparison to placebo. PDT consists of application of the photosensitizer 5-aminolevulinic acid followed by treatment with a blue light. PDT is used to treat pre-cancerous actinic keratosis on large areas of skin. These studies are a continuation of ongoing studies that indicate that the lipid mediator platelet-activating factor (PAF) is generated in skin following PDT, and that PDT suppresses the immune system. It is hypothesized that PDT-generated PAF results in the immunosuppression associated with PDT. Therefore, it is proposed that a treatment to block that immunosuppression could protect the patient undergoing PDT. Blockers of the PAF system are not currently commercially available. However research studies done at Wright State University using mice indicate that PAF- and PDT-induced immunosuppression is blocked by treatment with COX-2 inhibitors. This study is conducted as a proof of concept.

Study length and visit for subjects with actinic keratoses: The first part of the study is completed in 12 days then there are follow up visits at 6 and 12 months. There are a total of 6 separate visits to the research office.

Study length and visit for control subjects: The study is completed in 10 days. There are a total of 4 separate visits to the research office.

Photodynamic Therapy-Induced Immune Modulation: Part III

Investigator will assess change through clinical laboratory values and reactions to skin testing.

Investigator will assess the number of actinic keratosis in the PDT-treated areas.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer	NCT03026140	Colon Carcinoma	Nivolumab Ipilimumab Celecoxib 200mg BMS-986253 BMS-986016	18 Years -	The Netherlands Cancer Institute
Possible Protective Effect of Celecoxib Against Capecitabine Induced Hand and Foot Syndrome in Patients With Colorectal Cancer	NCT05327751	Hand and Foot S... Erythrodysesthe... HFS Colorectal Canc...	Celecoxib 200mg Capecitabine-ba...	18 Years - 65 Years	Tanta University
Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer	NCT03026140	Colon Carcinoma	Nivolumab Ipilimumab Celecoxib 200mg BMS-986253 BMS-986016	18 Years -	The Netherlands Cancer Institute
Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer	NCT03026140	Colon Carcinoma	Nivolumab Ipilimumab Celecoxib 200mg BMS-986253 BMS-986016	18 Years -	The Netherlands Cancer Institute
Photodynamic Therapy-Induced Immune Modulation: Part III	NCT03643744	Actinic Keratos... Photodynamic Th...	Celecoxib 200mg Placebo	45 Years -	Wright State University
Photodynamic Therapy-Induced Immune Modulation: Part III	NCT03643744	Actinic Keratos... Photodynamic Th...	Celecoxib 200mg Placebo	45 Years -	Wright State University

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