Talazoparib + Radiation for Gynecologic Cancers

Recruiting at 1 trial location

Overseen By Lilie Lin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inhibitors, P-gp inhibitors

Disqualifiers: Ascites, Hepatic metastases, Brain metastases, others

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

Compensation: Varies

Number of Visits: 6

Duration: 8 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of combining a new drug, talazoparib, with radiation therapy to treat gynecologic cancers that have recurred after previous treatment. Talazoparib may slow or stop cancer cell growth, while radiation therapy aims to kill cancer cells and shrink tumors. The trial seeks to determine the optimal dose and identify any side effects. Suitable candidates for this trial have recurrent ovarian, fallopian tube, primary peritoneal, endometrial, vaginal, or cervical cancer in the abdomen and pelvis, with no active spread elsewhere. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires participants to stop taking any cytotoxic chemotherapeutic agents, immunotherapy, biologic therapy, and targeted therapies at least three weeks before starting the study treatment. Additionally, you must avoid certain medications that interact with the study drug, such as CYP3A4 inhibitors and P-gp inhibitors or inducers.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that talazoparib, when combined with radiation therapy, has been studied to assess its safety and tolerability. These studies aim to determine the optimal dose and evaluate patient responses to the treatment. The FDA has already approved talazoparib for other uses, indicating its established safety. However, adding radiation might affect its tolerability.

Radiation therapy has treated various cancers for many years. It is generally well-tolerated but can cause side effects like fatigue or skin changes at the application site.

In summary, both talazoparib and radiation therapy have undergone safety studies. Talazoparib's previous approval for other conditions supports its safety, but researchers continue to study its combination with radiation carefully. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for gynecologic cancers typically involve surgery, chemotherapy, or standard radiation therapy. However, talazoparib is unique because it is a PARP inhibitor, a type of drug that blocks a protein used by cells to repair damage. This is particularly exciting because when combined with radiation therapy, it can enhance the treatment's ability to damage cancer cells while sparing normal ones, potentially improving outcomes. Researchers are excited because this combo could offer more effective treatment options, especially for patients who may not respond well to traditional therapies.

What evidence suggests that talazoparib combined with radiation therapy might be an effective treatment for gynecologic cancers?

Research shows that talazoparib, a type of drug, can block certain enzymes that help tumor cells grow, making it promising for treating ovarian cancer and possibly other gynecologic cancers. In this trial, participants will receive a combination of talazoparib and radiation therapy. Studies suggest that using talazoparib with radiation therapy might improve treatment results. Radiation therapy uses high-energy rays to kill cancer cells and shrink tumors. Combining these treatments aims to more effectively target and destroy cancer cells. Early findings support this approach for managing recurring gynecologic cancers. ^{5 6 7 8 9}

Who Is on the Research Team?

Lilie L Lin

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with certain types of recurrent gynecologic cancers, including ovarian, fallopian tube, primary peritoneal, endometrial, vaginal or cervical cancer. Participants must have adequate blood counts and organ function and not be pregnant or breastfeeding. They should agree to use effective birth control if applicable and not have any serious medical conditions that could interfere with the study.

Inclusion Criteria

I have a tumor that can be measured and has not been treated with radiation.

Your recent blood test does not show signs of a specific type of blood disorder called myelodysplastic syndrome or acute myeloid leukemia.

Your serum creatinine level is not more than 1.5 times the upper limit of normal.

Exclusion Criteria

I am not taking medications like ketoconazole or ritonavir.

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

My cancer has returned in the vagina only, with no spread to lymph nodes or elsewhere.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talazoparib orally once daily and undergo radiation therapy 5 days a week for up to 7 weeks

8 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Visits at 1, 3, 6, 9, and 12 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy
• Talazoparib

Trial Overview The trial is testing the combination of a drug called Talazoparib with radiation therapy to see how well they work together in treating recurrent gynecologic cancers. The goal is to determine the best dose of Talazoparib when used with radiation therapy and assess their effectiveness.

How Is the Trial Designed?

Group I: Treatment (talazoparib, radiation therapy) Experimental Treatment 3 Interventions

Patients receive talazoparib PO QD beginning on days -10 to -7 and continuing for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy 5 days a week (Monday-Friday) for up to 7 weeks.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Intensity-modulated radiotherapy (IMRT) for cervical cancer has been shown to reduce gastrointestinal toxicity while allowing for higher doses of radiation to be targeted at tumors, improving treatment safety.

Individualized, image-guided brachytherapy enhances the precision of high-dose radiation delivery, adapting to the tumor's specific shape and size, which may lead to better tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy of Cervical Cancer. Vordermark, D.[2017]

In a study involving 42 cervical cancer patients, combining image-guided radiation therapy (IGRT) with high-dose-rate intracavitary brachytherapy (ICBT) improved the dose distribution to the tumor while reducing exposure to surrounding healthy tissues, such as the bladder and rectum.

The results showed that while the target dose to the high-risk clinical target volume (HRCTV) was similar between the combined treatment and optimized ICBT alone, the combined approach significantly increased the dose to intermediate-risk areas and decreased the dose to critical organs, suggesting a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided radiation therapy boost in combination with high-dose-rate intracavitary brachytherapy for the treatment of cervical cancer. Wang, X., Li, J., Wang, P., et al.[2022]

Stereotactic radiosurgery (SRS) has been shown to be a safe and effective treatment for various gynecologic cancers, including cervical, endometrial, vulvar, vaginal, and ovarian cancers, based on a review of 20 case series and clinical trials from 1993 to 2013.

SRS is particularly indicated for patients with non-central pelvic recurrences, complex or non-resectable disease, and solitary brain metastases, making it a promising second-line treatment option for those who cannot undergo standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of stereotactic radiosurgery in the treatment of gynecologic malignancies: A review. Long, B., Eskander, RN., Tewari, KS.[2021]

In a study of 15,905 women with invasive cervical cancer treated with various radiation techniques, stereotactic body radiotherapy (SBRT) showed comparable overall survival to brachytherapy, indicating it may be a viable treatment option.

In contrast, intensity-modulated radiation therapy (IMRT) was associated with significantly worse overall survival compared to brachytherapy, suggesting that IMRT may not be as effective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy, Intensity-Modulated Radiation Therapy, and Brachytherapy Boost Modalities in Invasive Cervical Cancer: A Study of the National Cancer Data Base. OʼDonnell, B., Shiao, JC., Pezzi, TA., et al.[2022]

Intensity Modulated Radiotherapy (IMRT) effectively targets endometrial cancer while minimizing damage to surrounding healthy tissues, such as the kidneys, which is crucial for patients with unique anatomical challenges.

In a case study of a 50-year-old patient treated for endometrial cancer, IMRT allowed for successful treatment without relapse and preserved normal kidney function, highlighting its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity Modulated Radiotherapy (IMRT) in the postoperative treatment of an adenocarcinoma of the endometrium complicated by a pelvic kidney. Castilho, MS., Jacinto, AA., Viani, GA., et al.[2018]

In a study of 117 patients with stage I-II endometrial cancer, a higher dose schedule of 24 Gy delivered in four fractions (C2) resulted in significantly lower rates of late vaginal toxicity compared to a lower dose schedule of 21 Gy in three fractions (C1).

The analysis also indicated that older age and the fractionation schedule were significant factors associated with toxicity, while the treatment showed high survival rates, with 96.6% local relapse-free survival at three years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EROS 2.0 study: evaluation of two interventional radiotherapy (brachytherapy) schedules for endometrial cancer: a comparison of late vaginal toxicity rates. Lancellotta, V., Macchia, G., Dinapoli, N., et al.[2022]

The study demonstrated that combining weekly paclitaxel chemotherapy with postoperative radiotherapy is a safe and feasible treatment for high-risk endometrial cancer, with mild hematological toxicity and manageable side effects in 13 patients.

While the treatment was well-tolerated, further prospective clinical studies are needed to assess its impact on long-term survival rates in patients with high-risk endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant radiotherapy and paclitaxel for high-risk endometrial cancer: first feasibility study. Frigerio, L., Mangili, G., Aletti, G., et al.[2015]

In a study of 11 gynecologic cancer patients who could not tolerate brachytherapy, stereotactic body radiotherapy (SBRT) was administered with a median dose of 25 Gy in five fractions, showing promising outcomes with eight patients alive at last follow-up.

The treatment demonstrated acceptable toxicity levels, with only two cases of acute toxicity and one case of late toxicity, suggesting that SBRT could be a safe alternative for patients who cannot undergo traditional brachytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy as an alternative to brachytherapy in gynecologic cancer. Kubicek, GJ., Xue, J., Xu, Q., et al.[2022]

Image-guided Radiotherapy (IGRT) enhances the effectiveness of Intensity-Modulated Radiotherapy (IMRT) by addressing the challenges of organ and target motion in pelvic treatments, which is crucial for safely delivering higher doses to cervical cancer patients.

Implementing IGRT solutions is essential to minimize the risk of geographic miss targeting and overdose to organs at risk, thereby improving treatment outcomes and reducing toxicity in cervical cancer radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Problems and solutions in IGRT for cervical cancer. Ríos, I., Vásquez, I., Cuervo, E., et al.[2020]

Intensity modulated radiotherapy (IMRT) significantly reduces the volume of non-cancerous rectum and small bowel tissues exposed to radiation compared to conventional three-dimensional conformal radiotherapy (3D-CRT), with reductions of up to 39.5% for rectum at higher doses (≥30 Gy).

Patients treated with IMRT did not experience higher rates of acute or chronic toxicities compared to those treated with 3D-CRT, indicating that IMRT is a safer option for delivering high doses of radiation in gynecologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy in patients with gynecologic malignancies: a systematic review and meta-analysis. Yang, B., Zhu, L., Cheng, H., et al.[2022]

Intensity-modulated radiation therapy (IMRT) is being explored as a way to enhance the effectiveness of conventional radiation therapy for gynecologic cancers while potentially allowing for higher doses due to reduced toxicity.

The report discusses both preclinical studies and clinical experiences, indicating a comprehensive approach to evaluating IMRT's safety and efficacy in treating these malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy in gynecologic malignancies. Mundt, AJ., Roeske, JC., Lujan, AE.[2019]

Intraoperative radiation therapy (IORT) can enhance local tumor control and overall survival in women with advanced gynecologic cancers, particularly those with pelvic sidewall or para-aortic nodal recurrences.

IORT is especially beneficial for patients with microscopic residual disease after surgical debulking, as it allows for higher radiation doses to the tumor while protecting surrounding healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of intraoperative radiation therapy (IORT) in the treatment of locally advanced gynecologic malignancies. del Carmen, MG., McIntyre, JF., Goodman, A.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7065668/

Intensity Modulated Radiation Therapy and Image-Guided ... This study reported long-term outcomes of patients with cervical cancer who were treated with intensity modulated radiation therapy and 3-dimensional (3D) image ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825813003089

Intensity modulated radiotherapy in gynecologic cancers With increased accuracy of treatment delivery comes the need for greater accuracy in target delineation and incorporation of motion to prevent marginal misses.

3. thegreenjournal.com thegreenjournal.com/issue/S0167-8140(25)X0003-7?pageStart=13

May 2025 Chemoradiotherapy combined with image-guided adaptive brachytherapy for locally advanced cervical cancer results in sustained outcomes beyond 5 years.

4. practicalradonc.org practicalradonc.org/article/S1879-8500(22)00273-9/fulltext

Radiation Therapy for Endometrial Cancer: An American ... With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and ...

5. nature.com nature.com/articles/s41598-024-85074-9

A comparative analysis of toxicity and treatment outcomes ... To investigate the clinical benefits of ART, we have collected data from 115 cervical cancer patients who underwent radical radiotherapy at our ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10789959/

Intensity-Modulated Radiation Therapy for Uterine Cervical ... Significant reduction in pelvic bone marrow (BM) irradiation results in significantly less incidence of anemia and thrombocytopenia in cervical cancer patients ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053429606000038

Intensity-Modulated Radiation Therapy for Gynecologic ... This article reviews the potential pitfalls and hazards of IMRT techniques on patient safety and treatment efficacy. In addition, the article describes multiple ...

8. ascopubs.org ascopubs.org/doi/10.1200/GO.23.00478

Longitudinal Costs of Image-Guided Intensity-Modulated ... The PARCER trial provided level I evidence for image-guided intensity-modulated radiation therapy (IG-IMRT) in patients with cervical cancer ...

9. international-journal-of-gynecological-cancer.com international-journal-of-gynecological-cancer.com/article/S1048-891X(24)00117-8/fulltext

Intensity modulated radiation therapy boost in locally ... The goal of our study was to determine whether an intensity modulated radiation therapy (IMRT) boost is feasible in patients unfit for brachytherapy.