G-CSF Omission for Breast Cancer

(REaCT-OGF Trial)

Recruiting at 2 trial locations

Overseen By Carol Stober

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must be taking: G-CSF

Disqualifiers: Metastatic cancer, Hypersensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

242 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of skipping granulocyte colony-stimulating factor (G-CSF) injections during a specific breast cancer treatment. G-CSF usually helps prevent infections during chemotherapy. In this study, some participants will continue using G-CSF, while others will not, to determine if omitting it makes a difference. Individuals with early-stage or locally-advanced breast cancer receiving a certain type of chemotherapy might qualify if they can give verbal consent and complete questionnaires in English or French. As a Phase 4 trial, this research aims to understand how an already FDA-approved treatment benefits more patients.

Do I have to stop taking my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It focuses on whether or not to use G-CSF during a specific chemotherapy treatment.

What is the safety track record for these treatments?

Research has shown that skipping granulocyte colony-stimulating factor (G-CSF) in some breast cancer treatments might be safe. One study found that omitting G-CSF did not cause treatment delays or increase side effects. Patients who did not receive G-CSF maintained their treatment schedules without issues.

While G-CSF is generally safe, it can cause side effects like bone pain. Avoiding G-CSF might prevent these side effects while maintaining the effectiveness of cancer treatment. Overall, evidence suggests that not using G-CSF could be a well-tolerated option for patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the omission of Granulocyte Colony-Stimulating Factor (G-CSF) in breast cancer treatment because it could simplify the chemotherapy process. Typically, G-CSF injections, like filgrastim or pegfilgrastim, are given after chemotherapy to help boost white blood cell counts and reduce infection risk. However, omitting G-CSF could mean fewer side effects and less burden from additional treatments. This approach might streamline care and improve quality of life for patients undergoing paclitaxel chemotherapy without compromising safety or effectiveness.

What evidence suggests that omitting G-CSF might be effective for breast cancer patients receiving paclitaxel chemotherapy?

Research has shown that certain medications, known as granulocyte colony-stimulating factors (G-CSF), help reduce the risk of febrile neutropenia (FN). FN, a condition where low white blood cell counts cause a fever, often occurs in patients receiving chemotherapy. Studies indicate that G-CSF can nearly halve the risk of FN for these patients. In this trial, one group of participants will receive G-CSF injections after each cycle of paclitaxel chemotherapy. Another group will not receive G-CSF to explore whether it's safe to omit G-CSF in certain breast cancer treatments. The goal is to determine if patients can avoid the possible side effects of G-CSF without increasing their risk of FN. While G-CSF has clear benefits, this trial explores whether not using it might be just as effective in specific cases. ^{2 4 5 6 7}

Who Is on the Research Team?

Xinni Song

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for early-stage or locally-advanced breast cancer patients who are about to receive DD-AC/T chemotherapy and need drugs to prevent infection due to low white blood cell counts. Participants must be able to consent and complete questionnaires in English or French, but can't join if they have metastatic cancer, past severe reactions to G-CSF, recent chemo within 5 years, or other serious health issues.

Inclusion Criteria

Able to provide verbal consent

I can complete questionnaires in English or French.

I am getting specific chemotherapy for breast cancer and need medicine to prevent infection.

Exclusion Criteria

Patients with uncontrolled inter-current illness that would limit compliance with study requirements or other significant diseases or disorders that, in the investigator's opinion, would exclude the subject from participating in the study

You are allergic to filgrastim or pegfilgrastim.

I have had chemotherapy in the past 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy Treatment

Participants receive 4 cycles of adriamycin and cyclophosphamide followed by 4 cycles of paclitaxel using a dose-dense schedule

16 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of treatment-related hospitalizations and ER visits

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Granulocyte Colony-Stimulating Factor (G-CSF)
• Omission of Granulocyte Colony-Stimulating Factor (G-CSF)

Trial Overview The study is testing whether it's safe for breast cancer patients on the paclitaxel part of their DD-AC/T chemotherapy regimen to skip taking G-CSF—a drug usually given to boost white blood cells and prevent infections. Patients will either continue with G-CSF as usual or go without it during this phase of treatment.

How Is the Trial Designed?

Group I: Omission of G-CSF Experimental Treatment 1 Intervention

Omission of G-CSF injections after each cycle of paclitaxel chemotherapy.

Group II: Receive G-CSF Active Control 1 Intervention

Receive G-CSF injections (either filgrastim or pegfilgrastim) after each cycle of paclitaxel chemotherapy.

Omission of Granulocyte Colony-Stimulating Factor (G-CSF) is already approved in United States, European Union for the following indications:

Approved in United States as Paclitaxel for:

• Advanced ovarian cancer
• Metastatic breast cancer
• Non-small cell lung cancer
• Kaposi sarcoma

Approved in European Union as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi sarcoma

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Published Research Related to This Trial

In a phase II study involving 28 patients with metastatic breast cancer, Taxol (paclitaxel) demonstrated a high response rate, with 62% of patients showing objective responses, including 12% achieving complete responses.

The use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) effectively reduced the severity and duration of neutropenia, a common side effect of chemotherapy, allowing 79% of patients to avoid hospitalization for neutropenic fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer. Reichman, BS., Seidman, AD., Crown, JP., et al.[2017]

In a study involving 36 women with metastatic breast cancer, the use of recombinant granulocyte-colony stimulating factor (rGCSF) as primary prophylaxis effectively reduced the incidence of febrile neutropenia to 14% during chemotherapy with docetaxel and doxorubicin.

The treatment was found to be safe, with common side effects including leukocytosis and bone pain, but it did not lead to any chemotherapy dose reductions, and patients reported improved emotional functioning and reduced pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and efficacy study of the recombinant granulocyte colony-stimulating factor for prevention of neutropenia and neutropenia-related complications in women with metastatic breast cancer receiving docetaxel/doxorubicin]. Liutkauskiene, S., Sveikata, A., Juozaityte, E., et al.[2018]

In a study of 47 ovarian cancer patients, using flexible dosing of granulocyte colony-stimulating factor (G-CSF) allowed for maintaining higher doses of taxol, which is associated with improved treatment efficacy, in 81% of patients.

The approach of increasing G-CSF dosage instead of reducing taxol after episodes of febrile neutropenia helped prevent further complications and may lower the risk of recurrence of neutropenia, suggesting that flexible G-CSF dosing could enhance the effectiveness of taxol therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flexible granulocyte colony-stimulating factor dosing in ovarian cancer patients who receive dose-intense taxol therapy. Link, CJ., Bicher, A., Kohn, EC., et al.[2021]

In a study of 56 patients with metastatic breast cancer who had previously been treated with anthracyclines, docetaxel showed a high overall response rate of 53%, indicating its effectiveness even in challenging cases.

The use of prophylactic granulocyte colony-stimulating factor significantly reduced severe neutropenia and neutropenic fever, while lower rates of fluid retention syndrome were observed with dexamethasone, suggesting that these supportive treatments can help manage docetaxel's side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and activity of docetaxel in anthracycline-pretreated breast cancer patients: a phase II study. Ferraresi, V., Milella, M., Vaccaro, A., et al.[2019]

In a study of 61 early breast cancer patients treated with accelerated paclitaxel without routine prophylactic GCSF, 69% did not require GCSF, indicating that it may not be necessary for all patients.

The treatment was safe, with no cases of neutropenic sepsis, and only a small percentage (10%) requiring secondary GCSF for severe neutropenia, suggesting that avoiding GCSF can reduce costs and side effects without compromising patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine prophylactic granulocyte colony stimulating factor (GCSF) is not necessary with accelerated (dose dense) paclitaxel for early breast cancer. Arnedos, M., Sutherland, S., Ashley, S., et al.[2015]

The study evaluated the safety and efficacy of recombinant granulocyte colony-stimulating factor (rG-CSF) in preventing neutropenia-related complications in 50 patients with metastatic breast cancer undergoing chemotherapy, showing that rG-CSF is effective in reducing the incidence of febrile neutropenia.

Despite some adverse events, including leukocytosis and bone pain, rG-CSF demonstrated a favorable safety profile and significantly decreased the risk of severe neutropenia, indicating its potential as a supportive treatment during myelosuppressive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label multicenter safety, tolerability, and efficacy study of recombinant granulocyte colony-stimulating factor in the prevention of neutropenic complications in breast cancer patients. Sveikata, A., Liutkauskienė, S., Juozaitytė, E., et al.[2018]

Recombinant human granulocyte colony-stimulating factor (G-CSF) has been shown to effectively support cancer patients by allowing them to receive chemotherapy without significant dose reductions or delays, while also reducing the risk of febrile neutropenia.

G-CSF acts quickly to enhance neutrophil production, reducing the maturation and release time of these immune cells from 4-5 days to just 1-2 days, and has minimal side effects, making it a preferred treatment in oncology settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human granulocyte colony-stimulating factor in the management of cancer patients: five years on. Bronchud, MH.[2018]

A systematic review of 61 randomized controlled trials involving over 9,000 patients showed that granulocyte colony-stimulating factor (G-CSF) significantly reduces all-cause mortality in patients receiving chemotherapy, with a relative risk of 0.93.

The most substantial mortality reduction was noted in studies using dose-dense chemotherapy schedules, indicating that G-CSF support can enhance treatment effectiveness and safety in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Lyman, GH., Dale, DC., Culakova, E., et al.[2022]

In a study of 1447 chemotherapy patients, initiating G-CSF (filgrastim) within 24-72 hours post-chemotherapy was found to be effective and safe for preventing chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN).

Patients who received G-CSF on the same day as chemotherapy had similar outcomes to those who followed the recommended guidelines, but those who started treatment late (more than 72 hours after chemotherapy) had worse odds of experiencing severe CIN episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (Zarzio®) initiated "same-day" ( 72 h): findings from the MONITOR-GCSF study. Ludwig, H., Gascón, P., Bokemeyer, C., et al.[2020]

Citations

1. ctv.veeva.com ctv.veeva.com/study/evaluating-omission-of-granulocyte-colony-stimulating-factors-in-breast-cancer-patients-receiving-pa

Evaluating Omission of Granulocyte Colony-stimulating ... The goal of this randomized, pragmatic clinical trial is to evaluate the omission of granulocyte colony-stimulating factors (G-CSF) in ...

2. withpower.com withpower.com/trial/phase-4-breast-neoplasms-3-2023-b6992

G-CSF Omission for Breast Cancer (REaCT-OGF Trial) The use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) effectively reduced the severity and duration of neutropenia, a common side effect ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9633501/

G-CSF use in breast cancer patients FN can be prevented with granulocyte-colony stimulating factors (G-CSFs). Guidelines recommend primary G-CSF use for patients receiving either high (> 20%) FN ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S096097762100028X

Long-term patient reported outcomes and hematologic ... Granulocyte colony-stimulating factors (G-CSF) are able to reduce the incidence of FN, with the relative risk of FN being almost halved among patients receiving ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05753618

Evaluating Omission of Granulocyte Colony-stimulating ... The goal of this randomized, pragmatic clinical trial is to evaluate the omission of granulocyte colony-stimulating factors (G-CSF) in breast cancer patients ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05753618

Evaluating Omission of Granulocyte Colony-stimulating ... The goal of this randomized, pragmatic clinical trial is to evaluate the omission of granulocyte colony-stimulating factors (G-CSF) in breast cancer ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27721193/

Variation in the use of granulocyte-colony stimulating factor ... We identified substantial variation in the use of G-CSF within the practice. However, omission of G-CSF was not associated with treatment delays or adverse ...