Sequential vs Concurrent Chemotherapy with Radiation for Breast Cancer

Not currently recruiting at 10 trial locations

Overseen By Nikki Barrow

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Richard Zellars

Must be taking: Chemotherapy

Disqualifiers: Neoadjuvant therapy, Squamous cancer, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if administering partial breast irradiation (a type of radiation therapy) and chemotherapy simultaneously results in the same side effects and outcomes as administering them separately. It targets women who have had breast cancer removed and require radiation to the breast. Eligibility requires a breast tumor no larger than 4 cm, no more than three positive lymph nodes, and a doctor's recommendation for chemotherapy. Participants will be randomly assigned to receive treatments either together or separately, with two-thirds likely to receive the combined method. This study could help improve treatment plans for future patients. As an unphased trial, it offers a unique opportunity to contribute to research that could refine and enhance future breast cancer treatment strategies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. It's best to discuss your specific situation with the study team or your doctor.

What prior data suggests that this new method is safe?

Research has shown that partial breast irradiation (PBI) is usually easy for patients to handle, causing fewer serious side effects than treatments targeting the whole breast. Most patients experience fewer early serious side effects.

When combined with chemotherapy, studies have found PBI to be quite safe. Patients receiving both treatments simultaneously generally did well without many severe problems. This combination might even help control cancer more effectively, both in the breast and throughout the body.

Based on past research, these treatments appear safe for most people. However, discussing options with a doctor is always important to determine the best approach. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial comparing sequential versus concurrent chemotherapy with radiation for breast cancer because it explores the timing of treatments to potentially enhance effectiveness. Unlike standard treatments that often separate chemotherapy and radiation, this trial examines the impact of combining them concurrently. The concurrent approach could maximize tumor control by synchronizing the effects of both therapies, potentially leading to better outcomes. This strategy might also reduce the overall treatment time, offering a more convenient option for patients.

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

Research has shown that treating early-stage breast cancer with partial breast irradiation (PBI) can be as effective as whole breast irradiation (WBI), but with fewer side effects. Studies indicate that PBI offers similar long-term results to WBI, especially with newer methods.

In this trial, one group of participants will receive PBI alone, while another group will receive PBI combined with chemotherapy. Early research suggests that administering both treatments simultaneously might be as effective, or even better, for certain types of breast cancer. Initial studies found that this combined treatment may help prevent cancer recurrence in the same area.

Overall, using both treatments together could lead to similar or better outcomes compared to administering radiation and chemotherapy separately. ^{6 7 8 9 10}

Who Is on the Research Team?

Richard Zellars, MD

Principal Investigator

Indiana University School of Medicine, Indiana University Simon Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 who've had breast cancer surgery with no remaining margins, have a performance status indicating they can carry out light activity, and need chemotherapy. They must not be pregnant, use effective birth control if of child-bearing potential, and have invasive adenocarcinoma of the breast treatable with specific chemo regimens.

Inclusion Criteria

My oncologist has recommended chemotherapy for me.

I have been treated with specific chemotherapy regimens before joining.

My breast cancer is confirmed to be invasive adenocarcinoma.

Exclusion Criteria

I have received initial treatment with chemotherapy or hormone therapy for my current cancer.

I had breast cancer on the same side and have been cancer-free for less than 5 years.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive partial breast irradiation and chemotherapy, either concurrently or sequentially

6-7 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6-7 months

Long-term follow-up

Participants are monitored for long-term toxicities and tumor recurrence

60 months

What Are the Treatments Tested in This Trial?

Interventions

• Concurrent Chemotherapy
• Partial Breast Irradiation
• Sequential Chemotherapy

Trial Overview

The study compares two methods: partial breast irradiation (PBI) given at the same time as chemotherapy versus PBI followed by chemotherapy. Women will be randomly assigned to one of these treatments in a larger ratio favoring the new concurrent method.

How Is the Trial Designed?

Group I: PBI with chemotherapy Experimental Treatment 1 Intervention

270 cGy (centigray) x 15 concurrent with chemotherapy of the treating medical oncologist's choice

Group II: PBI Active Control 1 Intervention

270 cGy (centigray) x 15

Partial Breast Irradiation is already approved in United States, European Union for the following indications:

Approved in United States as Partial Breast Irradiation for:

• Early-stage invasive breast cancer
• Ductal carcinoma in situ (DCIS)

Approved in European Union as Partial Breast Irradiation for:

• Early-stage invasive breast cancer
• Ductal carcinoma in situ (DCIS)

Who Is Running the Clinical Trial?

Richard Zellars

Lead Sponsor

Trials

2

Recruited

100+

Published Research Related to This Trial

In a study of 55 patients undergoing accelerated partial breast irradiation (APBI), common acute toxicities included moderate breast enlargement (22% of patients) and severe skin toxicity (27%), with symptoms typically resolving by 8 weeks post-treatment.

Despite the reported toxicities, the study found no significant correlation between dosimetric parameters and the severity of symptoms, indicating that further research is needed to better understand how treatment planning may influence patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Partial Breast Irradiation: Association of Dosimetric Parameters With Patient-Reported Outcomes. Lapen, K., Fiasconaro, M., Zhang, Z., et al.[2023]

Accelerated partial breast irradiation (APBI) using either low-dose-rate (LDR) or high-dose-rate (HDR) techniques showed modest and acceptable toxicity rates in a study of 99 women, with only 3% of HDR patients experiencing severe toxicity compared to 9% in the LDR group.

The study indicates that while APBI is effective in reducing treatment time to 4-5 days compared to conventional methods, patients receiving chemotherapy had a higher rate of Grade 3 toxicity, highlighting the need for careful monitoring in such cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: toxicity analysis of RTOG 95-17. Kuske, RR., Winter, K., Arthur, DW., et al.[2022]

In a study of 157 older patients with low-risk breast cancer, both accelerated partial breast irradiation (APBI) and ultra-APBI (uAPBI) showed similar oncologic outcomes, with no significant differences in local or regional recurrence rates, disease-free survival, or overall survival.

Late toxicity and cosmetic results were also comparable between the two treatment methods, suggesting that uAPBI, which uses a single fraction of brachytherapy, is a safe and effective option for reducing treatment intensity in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APBI Versus Ultra-APBI in the Elderly With Low-Risk Breast Cancer: A Comparative Analysis of Oncological Outcome and Late Toxicity. Hannoun-Lévi, JM., Montagne, L., Sumodhee, S., et al.[2021]

In a study of 290 patients receiving accelerated partial breast irradiation (APBI) with a median follow-up of 8 years, the rate of ipsilateral breast tumor recurrence (IBTR) was significantly higher (6.2%) compared to 1.0% in 290 patients receiving whole breast irradiation (WBI), indicating a greater risk of recurrence with APBI.

Despite the higher recurrence rates, APBI was associated with significantly fewer toxicities, such as fatigue and skin reactions, suggesting that while APBI may pose a higher risk of cancer recurrence, it offers a more tolerable treatment experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single Institution Retrospective Comparison Study of Locoregional Recurrence After Accelerated Partial Breast Irradiation Using External Beam Fractionation Compared with Whole Breast Irradiation with 8 Years of Follow-Up. Shah, S., Kyrillos, A., Kuchta, K., et al.[2018]

Accelerated partial breast irradiation (APBI) is linked to a higher local recurrence rate of breast cancer compared to whole-breast irradiation (WBI), with a significant hazard ratio of 4.54 based on a meta-analysis of 1407 participants.

Despite the increased local recurrence with APBI, there were no significant differences in nodal recurrence, systemic recurrence, overall survival, or mortality rates between the two treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated partial irradiation for breast cancer: systematic review and meta-analysis of 8653 women in eight randomized trials. Marta, GN., Macedo, CR., Carvalho, Hde A., et al.[2022]

Accelerated partial breast irradiation (APBI) is a promising new radiotherapy method for breast cancer patients, showing local control rates comparable to traditional whole breast radiotherapy in recent studies.

Ongoing phase III trials are investigating the safety and efficacy of various APBI techniques to determine if they can effectively replace whole breast radiotherapy for women opting for breast conservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated partial breast irradiation: where do we stand? Dirbas, FM.[2019]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10370352/

Concurrent chemotherapy with partial breast irradiation in ...

This study suggests that PBICC may offer similar and possibly better outcomes in patients with TNBC compared to a retrospective cohort treated with WBIaC.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT01928589

Partial Irradiation and Sequential vs. Concurrent Chemo ...

In a small study at Johns Hopkins, women were treated with partial breast irradiation and chemotherapy given at the same time.

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redjournal.org

redjournal.org/article/S0360-3016(19)31538-X/fulltext

Outcomes from Two Phase I/II Trials of Partial-Breast ...

Concurrent chemotherapy and whole breast irradiation is associated with prohibitive toxicity. With the advent of PBI, concurrent therapy may ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00681993

Trial of Partial Breast Irradiation With Various Concurrent ...

Review of smaller studies suggests that PBI will prove to be comparable to WBI. Chemotherapy combined with radiation has been shown to increase local control in ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/jco.2012.30.15_suppl.1128

Phase I/II trial of partial breast irradiation (PBI) with various ...

Background: Potential benefits of concurrent chemo-radiation include: shorter duration of treatment, smaller interval between surgery and ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10129380/

CONcurrent ChEmotherapy and RadioTherapy in adjuvant ...

This phase 2 study evaluated the safety of adjuvant chemoradiation (CTRT) for breast cancer. From April 2019 to 2020, 60 patients with stage ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4324341/

Concurrent chemoradiotherapy for locally advanced breast ...

Chemotherapy concurrent with radiation has the potential to offer patients the combined benefits of improved local and distant disease control. In early breast ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S1526820921003529

Concurrent Chemo-radiation As a Means of Achieving ...

Combination cisplatin and 5-fluorouracil with concurrent radiation in non-metastatic inflammatory breast cancer (IBC) has been demonstrated to be safe, and ...

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redjournal.org

redjournal.org/article/S0360-3016(17)30510-2/fulltext

(P010) Concurrent Chemotherapy With Adjuvant Radiation ...

Conclusions. Concurrent chemoradiation for high-risk breast cancer was well tolerated in these high-risk patients. Efficacy cannot yet be determined from this ...

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ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e12534

Efficacy and safety of concurrent capecitabine ...

Conclusions: Capecitabine concurrent with radiotherapy appears to be very efficacious and safe in the adjuvant treatment of breast cancer, ...