What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as mFOLFOX, often include side effects like neuropathy, which can persist long-term in some patients. Other frequent adverse events include diarrhea, nausea, vomiting, fatigue, and hand-foot syndrome. Additionally, severe neutropenia is more common in females. In trials involving adenosine receptor antagonists like AB928, side effects may include gastrointestinal issues and potential cardiovascular events, although these were not significantly higher than in placebo groups.

What prior FDA approvals exist?

The FDA has approved several treatments for colorectal cancer, including chemotherapy regimens like FOLFOX (a combination of folinic acid, fluorouracil, and oxaliplatin) and targeted therapies such as bevacizumab (an anti-VEGF monoclonal antibody). Immunotherapies, particularly immune checkpoint inhibitors like pembrolizumab (anti-PD-1), have also been approved for certain cases of colorectal cancer, especially those with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). While specific FDA approvals for adenosine receptor antagonists in colorectal cancer are not mentioned, the ongoing trial with AB928 in combination with chemotherapy and radiotherapy represents a novel approach in this therapeutic area.

What other types of research exist?

Promising novel alternatives to AB928 for colorectal cancer patients include immune checkpoint inhibitors like pembrolizumab and nivolumab, especially for patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. Additionally, novel targeted therapies such as BRAF inhibitors (e.g., encorafenib) combined with EGFR inhibitors (e.g., cetuximab) for BRAF V600E-mutant colorectal cancer, and the use of tyrosine kinase inhibitors like regorafenib and trifluridine/tipiracil for refractory cases, are also promising options.

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Checkpoint Inhibitor

Immunotherapy + Chemotherapy for Rectal Cancer (PANTHER Trial)

Phase 2

Recruiting

Led By Encouse Golden, M.D., Ph.D.

Research Sponsored by Weill Medical College of Cornell University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥ 18 years

Rectal cancer amenable to total mesorectal excision

Must not have

≥4 regional lymph nodes each ≥10 mm on pelvic MRI

Prior treatment with an agent targeting the adenosine pathway

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial uses a combination of radiation therapy, medication, and chemotherapy to treat patients with advanced pelvic tumors. The goal is to shrink the tumors, kill cancer cells, and enhance the overall effectiveness of the treatment.

Who is the study for?

Adults with rectal cancer that hasn't spread or been treated yet can join this trial. They need to be in good health, not have had prior pelvic radiation or chemotherapy for rectal cancer, and agree to use contraception. Pregnant women, those with recent severe illnesses or allergies to similar drugs, and patients on certain medications are excluded.

What is being tested?

The study tests a combination of new drugs (Zimberelimab and Etrumadenant) with standard chemo (FOLFOX regimen) after initial short-course radiation therapy. The goal is to see if this combo is safe and works better for treating rectal cancer.

What are the potential side effects?

Possible side effects include reactions related to the immune system attacking normal cells, infusion-related reactions from the drug entering the body, blood disorders like anemia or clotting problems, fatigue, nausea, diarrhea, and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My rectal cancer can be surgically removed with a specific technique.

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I have not had radiation therapy to my pelvic area.

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I have not had chemotherapy or surgery for rectal cancer.

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My condition is located more than 5cm from the anal opening.

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My cancer is at a specific stage according to tumor size and lymph node involvement.

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My condition is confirmed rectal adenocarcinoma.

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My cancer has not spread to distant parts of my body.

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I am not on antibiotics for an infection.

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I am fully active or can carry out light work.

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I am not pregnant and agree to use birth control during the study.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have 4 or more large lymph nodes in my pelvis.

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I have been treated with medication targeting the adenosine pathway before.

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My cancer affects the edge of tissue removed during surgery.

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I can take pills without issues like swallowing difficulty or constant nausea.

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My cancer is suspected to be very advanced.

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I have had radiation therapy to my pelvic area before.

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My rectal cancer cannot be surgically removed due to its attachment to nearby structures.

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I am not on any other cancer treatments or experimental drugs.

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My rectal cancer has come back.

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I haven't taken strong medication or substances that affect liver enzymes recently.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 60 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of treated patients who achieve complete pathologic response

Secondary study objectives

Therapeutic procedure

Overall survival

Progression free survival

Side effects data

From 2013 Phase 3 trial • 397 Patients • NCT00004054

78%

Menopausal symptoms

60%

Urinary frequency

52%

Impotence

47%

Late RT Toxicity: Bladder: NOS

39%

Diarrhea NOS

27%

Late RT Toxicity: Bowel: NOS

26%

Fatigue

26%

Late RT Toxicity: Other GU: NOS

21%

Proctitis NOS

21%

Dysuria

14%

Libido decreased

14%

Dermatitis radiation NOS

12%

Late RT Toxicity: Other: NOS

12%

Late RT Toxicity: Other GI: NOS

12%

Hemoglobin decreased

12%

Alanine aminotransferase increased

Gynaecomastia

Urinary retention

Pain-other

Aspartate aminotransferase increased

Rectal bleeding

Constipation

Leukopenia NOS

Edema NOS

Hematuria present

Renal/GU-Other

Arthralgia

Blood creatinine increased

Dyspnea NOS

Dermatitis exfoliative NOS

Depression NEC

Nausea

Hyperglycemia NOS

Lymphopenia

Myalgia

Peripheral sensory neuropathy

Platelet count decreased

Hyponatremia

Hypocalcemia

Blood albumin decreased

Stomatitis

Weight decreased

Anorexia

Hematologic-Other

Neutropenia

Alopecia

100%

80%

60%

40%

20%

Study treatment Arm

Hormones and RT

Hormones and RT Plus Chemotherapy

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Radiation therapy and etrumadenant (AB928)Experimental Treatment4 Interventions

Enrolled patients will receive Radiation therapy of 25 Gy in 5 fractions along with etrumadenant 150mg oral drug taken once daily. this will then be followed by 9 cycles of FOLFOX in combination of etrumadenant and zimberelimab investigational drugs.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Radiation therapy

2013

Completed Phase 3

~2850

FOLFOX regimen

2009

Completed Phase 3

~2440

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for colorectal cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy, such as mFOLFOX, works by damaging the DNA of cancer cells, preventing them from dividing and growing. Targeted therapies, like bevacizumab, inhibit specific molecules involved in tumor growth and angiogenesis. Immunotherapy, including PD-1 inhibitors like AB122, enhances the immune system's ability to recognize and destroy cancer cells. Adenosine receptor antagonists like AB928 block adenosine signaling, which can suppress immune responses in the tumor microenvironment. These mechanisms are crucial for colorectal cancer patients as they offer multiple strategies to attack cancer cells, potentially improving treatment efficacy and patient outcomes.

Receptor tyrosine kinase inhibitors for the treatment of osteosarcoma and Ewing sarcoma.Disparity between Inter-Patient Molecular Heterogeneity and Repertoires of Target Drugs Used for Different Types of Cancer in Clinical Oncology.Compound-therapy based on cancer-immunity cycle: promising prospects for antitumor regimens.