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

Trial Summary

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.

What data supports the effectiveness of the treatment Talazoparib + Radiation for Gynecologic Cancers?

Research shows that various forms of radiation therapy, like intensity-modulated radiotherapy (IMRT) and intraoperative radiation therapy (IORT), can improve local tumor control and reduce side effects in gynecologic cancers. These techniques help target the cancer more precisely, sparing healthy tissue and potentially improving survival rates. ^{1 2 3 4 5}

Is the combination of Talazoparib and various forms of radiation therapy safe for treating gynecologic cancers?

Research on radiation therapy for gynecologic cancers, including methods like Intensity-Modulated Radiotherapy (IMRT) and Image-Guided Radiotherapy (IGRT), shows that these treatments can reduce certain side effects, like gastrointestinal issues, compared to older methods. However, radiation therapy can still cause a range of side effects, and safety depends on careful targeting and dose management. ^{5 6 7 8 9}

How is the Talazoparib + Radiation treatment different for gynecologic cancers?

The Talazoparib + Radiation treatment is unique because it combines a drug that targets cancer cell repair mechanisms with advanced radiation techniques to precisely target tumors while sparing healthy tissue. This approach aims to improve local tumor control and potentially enhance survival rates in patients with challenging gynecologic cancers. ^{4 5 10 11 12}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of talazoparib in combination with radiation therapy and to see how well they work in treating patients with gynecologic cancers that have come back after previous treatment (recurrent). Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving talazoparib in combination with radiation therapy may work better in treating patients with gynecologic cancers.

Research Team

Lilie L Lin

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Intensity Modulated Radiotherapy (IMRT) in the postoperative treatment of an adenocarcinoma of the endometrium complicated by a pelvic kidney. [2018]

3. Italy 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The role of intraoperative radiation therapy (IORT) in the treatment of locally advanced gynecologic malignancies. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Radiotherapy of Cervical Cancer. [2017]

6. Poland pubmed.ncbi.nlm.nih.gov

Problems and solutions in IGRT for cervical cancer. [2020]

7. Poland pubmed.ncbi.nlm.nih.gov

Image guided radiation therapy boost in combination with high-dose-rate intracavitary brachytherapy for the treatment of cervical cancer. [2022]

8. England 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. [2022]

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

Intensity-modulated radiation therapy in gynecologic malignancies. [2019]

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

Concomitant radiotherapy and paclitaxel for high-risk endometrial cancer: first feasibility study. [2015]

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

Use of stereotactic radiosurgery in the treatment of gynecologic malignancies: A review. [2021]

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

Stereotactic body radiotherapy as an alternative to brachytherapy in gynecologic cancer. [2022]