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 is a research study using Granulocyte Colony Stimulating Factor (GCSF) as a bone marrow stimulating agent for imaging to guide radiation treatment planning. G-CSF is a type of growth factor. Growth factors are proteins made in the body. G-CSF is a type of growth factor that makes the bone marrow produce white blood cells to reduce the risk of infection after some types of cancer treatment. GCSF is being given to stimulate the bone marrow to identify the active (blood cell producing regions) to better spare during pelvic radiation treatment planning.

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.

Is Image-Guided Radiation Therapy for Cervical Cancer using G-CSF treatments like Pegfilgrastim safe?

G-CSF treatments like Pegfilgrastim are generally safe and widely used to reduce chemotherapy-induced neutropenia (low white blood cell count). Common side effects include pain and fever, while serious side effects like aortitis (inflammation of the aorta) are rare. ^{1 2 3 4 5}

How does image-guided radiation therapy differ from other treatments for cervical cancer?

Image-guided radiation therapy for cervical cancer is unique because it uses advanced imaging techniques to precisely target the tumor, allowing for higher doses of radiation to be delivered directly to the cancer while minimizing damage to surrounding healthy organs. This approach improves pelvic control and survival rates compared to traditional radiation therapy. ^{6 7 8 9 10}

What data supports the effectiveness of the drug G-CSF (Granulocyte Colony Stimulating Factor) in treating cervical cancer?

The research indicates that the addition of GM-CSF (a similar growth factor to G-CSF) to chemotherapy in cervical cancer patients showed promising response rates and survival outcomes, suggesting potential benefits of using growth factors like G-CSF in treatment. ^{7 8 11 12 13}

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

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]

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]

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]

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]

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]

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]

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]

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 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 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 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]

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]

Citations

1. United States 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. [2019]

2. Netherlands 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Novel chemotherapy approaches in chemoradiation protocols. [2008]

4. Japan pubmed.ncbi.nlm.nih.gov

[Improvement in the effects of radiation therapy with BRM]. [2018]

5. Singapore pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. [2020]

6. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

Efficacy and safety of PEG-rhG-CSF in preventing chemoradiotherapy-induced neutropenia in patients with locally advanced cervical cancer. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pegfilgrastim-Induced Aortitis in a Patient with Small-Cell Lung Cancer Who Received Immunotherapy Combined with Chemotherapy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Pegfilgrastim. [2019]

9. England 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Pegfilgrastim; a neutrophil mediated granulocyte colony stimulating factor-expanding uses in cancer chemotherapy. [2022]

11. United States 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. [2022]

12. England 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. [2022]

13. Ireland pubmed.ncbi.nlm.nih.gov

Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. [2022]