Image-Guided Radiation Therapy for Cervical Cancer

Overseen By Camellia Djebroun

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Stanford University

Disqualifiers: Other cancer, Previous pelvic radiation, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 33 months

7 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for planning radiation treatment for cervical cancer using Granulocyte Colony Stimulating Factor (GCSF). GCSF stimulates the bone marrow to produce white blood cells, and in this study, it highlights active bone marrow areas to protect during radiation. The trial seeks to determine the optimal GCSF dose, with different groups receiving various dosages. Suitable candidates include those with gynecologic cancers, such as cervical or endometrial cancer, who are already undergoing pelvic radiation and chemotherapy. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking medical advancements.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this method is safe for guiding radiation therapy?

Research has shown that Granulocyte Colony Stimulating Factor (GCSF) is generally safe for people. Studies indicate that GCSF effectively prevents low white blood cell counts, known as neutropenia, during cancer treatment. This is important because low white blood cell counts can lead to infections.

In several studies, GCSF reduced the risk of these side effects in patients receiving treatment for cervical cancer. Most patients tolerated the treatment well. Reports of mild side effects occurred, but serious problems were rare.

Since this trial is in its early stages, it mainly focuses on finding the right dosage. So far, using GCSF in other situations has suggested it is safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for cervical cancer involve surgery, chemotherapy, or traditional radiation therapy. However, researchers are excited about the potential of using GCSF (Granulocyte Colony-Stimulating Factor) alongside image-guided radiation therapy. Unlike standard treatments, GCSF is known for boosting the body's production of white blood cells, which might enhance the effectiveness of radiation therapy by improving the body's ability to target cancer cells. This novel approach could lead to more precise and effective treatment options, potentially reducing side effects and improving outcomes for patients with cervical cancer.

What evidence suggests that this trial's treatments could be effective for cervical cancer?

Research has shown that Granulocyte Colony Stimulating Factor (GCSF) can benefit patients with cervical cancer by reducing the risk of severe neutropenia, a condition where white blood cell levels drop during cancer treatments. One study found that 83.33% of patients using GCSF completed their radiotherapy within the planned 8 weeks, compared to only 51.72% who did not use it. This finding suggests that GCSF can help patients adhere to their treatment schedules. In this trial, participants will receive GCSF in different dosing regimens to determine the optimal dose. Additionally, GCSF is considered safe and effective in preventing low white blood cell counts in patients receiving both chemotherapy and radiation therapy. ^{4 6 7 8 9}

Who Is on the Research Team?

Elizabeth A Kidd, MD

Principal Investigator

Stanford Universiy

Are You a Good Fit for This Trial?

This trial is for individuals with certain stages of cervical or endometrial cancer who haven't had pelvic radiation, other cancer treatments in the past 2 years, or conditions preventing chemotherapy. They must have good kidney and bone marrow function, an ECOG performance status of 0-2, and be able to consent.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document.

My blood tests show normal white cell and platelet counts.

My kidney function is within the normal range.

Exclusion Criteria

I cannot undergo chemotherapy due to a medical condition.

I have had radiation therapy to my pelvic area before.

You have received treatment for another type of cancer within the past two years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Phase I involves dose finding with GCSF in cohorts to determine the optimal dose for phase II

12 months

Weekly visits for CBC and differential checks

Treatment

Participants receive chemoradiation with GCSF at the optimal dose determined in phase I

33 months

Weekly visits for CBC and differential checks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GCSF

Trial Overview The study tests using GCSF (a growth factor that stimulates white blood cell production) along with FDG-PET/CT imaging to guide radiation therapy planning for better bone marrow sparing in treating cervical and endometrial cancers.

How Is the Trial Designed?

Group I: Phase II-G-CSF Experimental Treatment 1 Intervention

Phase 2 participants will be treated with the optimal dose of GCSF found in the phase 1 portion of the study.

Group II: Phase I -Dose finding, Cohort 3 Experimental Treatment 1 Intervention

Dosing will occur in cohorts of 3 patients, If 3 out of 3 patients achieve the target SUVmean, the GCSF dose will be 780 mcg x 1 day

Group III: Phase I -Dose finding, Cohort 2 Experimental Treatment 1 Intervention

Dosing will occur in cohorts of 3 patients, If 3 out of 3 patients achieve the target SUVmean, the GCSF dose will be 780 mcg x 2 days

Group IV: Phase I -Dose finding, Cohort 1 Experimental Treatment 1 Intervention

Dosing will occur in cohorts of 3 patients with the start at dose of GCSF will be 780 mcg x 3 days

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

The combination of weekly paclitaxel and cisplatin during radiation therapy shows promising efficacy in 'high-risk' cervical cancer patients, with an overall survival rate of 68% at a median follow-up of 58 months.

While hematologic toxicity was common, it was manageable and did not frequently cause treatment delays; however, significant late complications occurred in 52% of patients, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. Argenta, PA., Ghebre, R., Dusenbery, KE., et al.[2020]

Pegfilgrastim (Neulasta) is a long-acting form of granulocyte colony stimulating factor (G-CSF) that is as safe and effective as daily G-CSF injections in preventing chemotherapy-induced neutropenia, allowing for once-per-cycle administration.

This single-dose treatment not only reduces the incidence of neutropenia but also improves patients' quality of life by minimizing the need for daily injections, and it is currently licensed in the US for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegfilgrastim. Willis, F., Pettengell, R.[2019]

In a study of 44 cervical cancer patients, image-guided brachytherapy (IGBT) using a combination of MRI and CT planning resulted in a high mean dose to the high-risk clinical target volume (HRCTV) of 83.3 Gy, leading to a remarkable 97.7% complete response rate after treatment.

The two-year survival rates were promising, with 88% local control, 85% disease-specific survival, and 86% overall survival, indicating that this hybrid imaging approach is effective for treating cervical cancer, although further research is needed for long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-dimensional high dose rate intracavitary image-guided brachytherapy for the treatment of cervical cancer using a hybrid magnetic resonance imaging/computed tomography approach: feasibility and early results. Beriwal, S., Kannan, N., Kim, H., et al.[2022]

A 73-year-old man with small-cell lung cancer developed a rare case of aortitis after receiving pegfilgrastim, a medication used to boost white blood cell counts during chemotherapy, highlighting the potential serious side effects of G-CSF treatments.

The patient's aortitis symptoms resolved without corticosteroid treatment, suggesting that careful monitoring without immunosuppression may be a viable approach in similar cases, especially when avoiding further immunosuppression is critical.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegfilgrastim-Induced Aortitis in a Patient with Small-Cell Lung Cancer Who Received Immunotherapy Combined with Chemotherapy. Ito, T., Kanai, O., Saito, Z., et al.[2023]

In a study of 731 patients with locally advanced cervical cancer, image-guided brachytherapy (IGBT) combined with chemotherapy and external beam radiation therapy (EBRT) resulted in high local control rates of 91% at 3 years and 89% at 5 years, indicating its efficacy in treating this condition.

The treatment was associated with low rates of severe morbidity, with only 5-7% of patients experiencing grade 3-5 complications in bladder, gastrointestinal tract, and vaginal areas, suggesting that IGBT is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. Sturdza, A., Pötter, R., Fokdal, LU., et al.[2022]

In a study of 40 patients with locally advanced cervical cancer, the use of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) significantly reduced the incidence of severe neutropenia (grade 3-4) compared to standard short-acting rhG-CSF, with 0 cases in the PEG-rhG-CSF group versus 4 in the control group.

PEG-rhG-CSF not only lowered the overall rates of neutropenia (24.05% vs. 56.94%) but also prevented chemotherapy delays due to neutropenia, with no delays reported in the PEG-rhG-CSF group compared to 11.11% in the rhG-CSF group, indicating its efficacy in maintaining treatment continuity during chemoradiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of PEG-rhG-CSF in preventing chemoradiotherapy-induced neutropenia in patients with locally advanced cervical cancer. Li, W., Dong, M., Huang, S., et al.[2023]

In a study involving 228 patients with Stage IIIB cervical cancer, the combination of radiation therapy and LC9018 significantly enhanced tumor regression and prolonged survival compared to radiation therapy alone.

LC9018 also reduced the severity of radiation-induced leukopenia, suggesting it may help protect patients from some side effects of radiation therapy, with only mild side effects like fever and skin lesions reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of LC9018 combined with radiation therapy on carcinoma of the uterine cervix. A phase III, multicenter, randomized, controlled study. Okawa, T., Niibe, H., Arai, T., et al.[2022]

In a study of 60 cervical cancer patients undergoing chemoradiotherapy, the use of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) significantly reduced the incidence of severe neutropenia (grade 3-4) to 10% compared to 77.78% in the control group (P < 0.001).

PEG-rhG-CSF also decreased the incidence of grade 4 neutropenia and febrile neutropenia, leading to fewer delays in chemotherapy cycles, while the overall safety profile was better in the experimental group with fewer adverse events (55% vs. 94.44%, P = 0.003).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent chemoradiotherapy of cervical cancer. Zou, D., Guo, M., Zhou, Q.[2021]

Pegfilgrastim is as effective or even more effective than filgrastim in reducing chemotherapy-induced neutropenia, making it a strong option for patients undergoing cancer treatment.

One of the key benefits of pegfilgrastim is that it can be administered just once per chemotherapy cycle, which may improve patient compliance and enhance their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegfilgrastim; a neutrophil mediated granulocyte colony stimulating factor-expanding uses in cancer chemotherapy. Morishita, M., Leonard, RC.[2022]

In a phase III study involving 36 women with advanced cervical or vaginal cancer, the combination of MVAC chemotherapy (methotrexate, vinblastine, doxorubicin, and cisplatin) showed a high clinical response rate of 78%, while the addition of GM-CSF resulted in a lower response rate of 50%.

Despite significant toxicity, including over 40% of patients experiencing severe leukopenia and stomatitis, the median survival was promising at 13.8 months for MVAC and 16.0 months for MVAC + GM-CSF, indicating that this treatment regimen may be effective even with dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival of patients with advanced/recurrent carcinoma of cervix and vagina after neoadjuvant treatment with methotrexate, vinblastine, doxorubicin, and cisplatin with or without the addition of molgramostim, and review of the literature. Long, HJ., Rayson, S., Podratz, KC., et al.[2019]

Chemotherapy combined with radiation therapy has significantly improved overall survival rates in patients with locally advanced cervical carcinoma, with weekly cisplatin (40 mg/m²) showing the best response compared to other combinations.

Despite the exploration of various other cytotoxic and biologic agents, no treatment has proven to be more effective than weekly cisplatin in conjunction with radiotherapy, which remains the standard therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chemotherapy approaches in chemoradiation protocols. González-Cortijo, L., Carballo, N., González-Martín, A., et al.[2008]

Both volumetric-modulated arc therapy (VMAT) and helical tomotherapy (HT) provide effective coverage for target volumes in extended-field bone marrow-sparing radiotherapy for cervical cancer, ensuring good dose homogeneity and conformity while protecting surrounding organs.

VMAT is more efficient than HT, as it requires significantly fewer monitor units and shorter treatment times, making it a preferable option for patients undergoing this type of radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-field bone marrow sparing radiotherapy for primary chemoradiotherapy in cervical cancer patients with para-aortic lymphadenopathy: Volumetric-modulated arc therapy versus helical tomotherapy. Chen, JL., Wang, MC., Huang, YS., et al.[2021]

Sonifilan (SPG), a glucan from Schizophyllum commune, showed superior effects in controlling human uterine cervix cancer compared to radiation therapy alone, indicating its potential as an effective treatment option.

SPG not only enhanced the effectiveness of radiation therapy in reducing primary tumors but also significantly suppressed experimental lung metastasis, suggesting a synergistic effect when combined with radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Improvement in the effects of radiation therapy with BRM]. Inomata, T., Ogawa, Y., Nishioka, A., et al.[2018]

Citations

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The efficacy and safety of the prophylactic application of PEG ... Multiple studies have indicated that the prophylactic use of rhG-CSF can reduce the risk of severe neutropenia and febrile neutropenia (FN) [5,6 ...

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Prospective clinical study of the efficacy and safety ... Prophylactic application of PEG-rhG-CSF could reduce the incidence of leukopenia/neutropenia in cervical cancer during concurrent chemoradiotherapy.

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Pegylated recombinant human granulocyte colony-stimulating ... PEG-rhG-CSF is an effective and safe prophylactic treatment for neutropenia in patients with cervical cancer undergoing concurrent chemoradiotherapy.

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Pegylated recombinant human granulocyte colony ... Conclusion: The study demonstrates that PEG-rhG-CSF has significantly improved radiotherapy completion rates and reduced the incidence of grade ...

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Safety and efficacy of pegylated recombinant human ... Safety and efficacy of polyethylene glycol recombinant human granulocyte colony-stimulating factor in concurrent chemoradiotherapy for cervical cancer. Chin ...