What is the mechanism of action of this treatment?

Common treatments for colorectal cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy drugs like 5-fluorouracil (5-FU) and oxaliplatin work by interfering with DNA synthesis and cell division, leading to cancer cell death. Targeted therapies, such as cetuximab and bevacizumab, inhibit specific molecules involved in tumor growth and angiogenesis, respectively. Cetuximab targets the epidermal growth factor receptor (EGFR), while bevacizumab targets vascular endothelial growth factor (VEGF). Immunotherapy, including drugs like nivolumab, enhances the body's immune response against cancer cells by blocking inhibitory pathways like PD-1/PD-L1. These mechanisms are crucial for colorectal cancer patients as they offer multiple avenues to halt tumor progression and improve survival rates. In the context of cachexia management, investigational treatments like Ponsegromab, which potentially neutralizes GDF 15, aim to address the severe weight loss and muscle wasting associated with advanced cancer, thereby improving patients' quality of life.

What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as oxaliplatin, capecitabine, and bevacizumab, have several known side effects. Oxaliplatin can cause peripheral neuropathy, fatigue, and gastrointestinal issues like nausea and diarrhea. Capecitabine often leads to hand-foot syndrome, diarrhea, and mucositis. Bevacizumab, an anti-VEGF monoclonal antibody, is associated with hypertension, thromboembolic events, and gastrointestinal perforations. These side effects are important considerations when managing colorectal cancer and related conditions like cachexia.

What prior FDA approvals exist?

The FDA has approved several treatments for colorectal cancer, including regorafenib, which is used for previously treated metastatic colorectal cancer. Regorafenib is a multi-kinase inhibitor that targets angiogenic, stromal, and oncogenic receptor tyrosine kinases. While Ponsegromab specifically targets GDF 15 to manage cachexia, there are no direct FDA-approved treatments for colorectal cancer that target GDF 15. However, the focus on managing cachexia in cancer patients is an emerging area of interest, and future approvals may include drugs with similar mechanisms.

What other types of research exist?

Promising alternatives to Ponsegromab for managing cachexia in colorectal cancer patients include: 1) Masitinib, a tyrosine kinase inhibitor that targets neuroinflammatory processes and has shown benefits in ALS, which may translate to cachexia management. 2) Neurotrophic factor (NTF)-secreting mesenchymal stromal cells (MSC-NTF cells), which have shown potential in slowing disease progression and improving functional outcomes in ALS, suggesting possible benefits for cachexia. 3) Bevacizumab, an anti-VEGF monoclonal antibody, which has shown activity in various cancers and may help manage cachexia by targeting angiogenesis and tumor growth.

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Ponsegromab for Cachexia (PROACC-1 Trial)

Phase 2

Waitlist Available

Research Sponsored by Pfizer

Eligibility Criteria Checklist

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

Must have

Documented diagnosis of non-small cell lung, pancreatic, colorectal cancer

Cachexia defined by Fearon criteria

Must not have

Receiving tube feedings or parenteral nutrition at the time of Screening or Randomization

Cachexia caused by other reasons

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, week 12

Summary

This trial tests Ponsegromab, a new drug, on cancer patients who are losing weight and have high GDF 15 levels. The drug aims to lower GDF 15 to improve appetite and reduce weight loss.

Who is the study for?

This trial is for adults with non-small cell lung, pancreatic, or colorectal cancer who are experiencing cachexia (significant weight loss due to illness) as defined by Fearon criteria. They must have elevated GDF-15 protein levels and be able to consent to the study. People with tube feedings, other causes of cachexia, severe allergies to monoclonal antibodies, or poor kidney/liver function cannot join.

What is being tested?

The trial is testing the effectiveness and safety of a drug called Ponsegromab in comparison to a placebo in patients suffering from cancer-related cachexia. Participants will either receive Ponsegromab or a placebo without knowing which one they're getting.

What are the potential side effects?

Possible side effects of Ponsegromab may include allergic reactions similar to those seen with other monoclonal antibody therapies. Specific side effects are not listed but generally could range from mild infusion-related reactions to more serious organ-specific inflammation.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with lung, pancreatic, or colorectal cancer.

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I have significant weight loss and muscle loss.

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I have been diagnosed with lung, pancreatic, or colorectal cancer.

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I am capable of limited self-care.

Exclusion Criteria

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

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I am currently on tube feedings or IV nutrition.

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My weight loss is not due to cancer.

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My kidney or liver is not working properly.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, week 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, week 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, week 12 for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Change from baseline in anorexia/appetite; Nausea and vomiting; and Fatigue as measured by the Cancer Related Cachexia Symptom Diary (CRCSD)

Change from baseline in physical activity as measured with remote digital sensors

change from baseline in Functional Assessment of Anorexia-Cachexia Therapy (FAACT-ACS and FAACT-5IASS) scores

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Double-Blind ponsegromab Treatment medium dose followed by Open Label ponsegromab TreatmentExperimental Treatment1 Intervention

ponsegromab medium dose subcutaneous injection every 4 weeks

Group II: Double-Blind ponsegromab Treatment low dose followed by Open Label ponsegromab TreatmentExperimental Treatment1 Intervention

ponsegromab low dose subcutaneous injection every 4 weeks

Group III: Double-Blind ponsegromab Treatment high dose followed by Open Label ponsegromab TreatmentExperimental Treatment1 Intervention

ponsegromab high dose subcutaneous injection every 4 weeks

Group IV: Double-Blind Placebo Treatment followed by Open-Label ponsegromab TreatmentPlacebo Group1 Intervention

Match placebo subcutaneous injection every 4 weeks

0 / 7Eligibility 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 drugs like 5-fluorouracil (5-FU) and oxaliplatin work by interfering with DNA synthesis and cell division, leading to cancer cell death. Targeted therapies, such as cetuximab and bevacizumab, inhibit specific molecules involved in tumor growth and angiogenesis, respectively. Cetuximab targets the epidermal growth factor receptor (EGFR), while bevacizumab targets vascular endothelial growth factor (VEGF). Immunotherapy, including drugs like nivolumab, enhances the body's immune response against cancer cells by blocking inhibitory pathways like PD-1/PD-L1. These mechanisms are crucial for colorectal cancer patients as they offer multiple avenues to halt tumor progression and improve survival rates. In the context of cachexia management, investigational treatments like Ponsegromab, which potentially neutralizes GDF 15, aim to address the severe weight loss and muscle wasting associated with advanced cancer, thereby improving patients' quality of life.

Metabolic reprogramming in epithelial ovarian cancer.