Sequential vs Concurrent Chemotherapy with Radiation for Breast Cancer

Recruiting at 9 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

81 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Sequential vs Concurrent Chemotherapy with Radiation for Breast Cancer?

Research shows that accelerated partial breast irradiation (APBI), a component of the treatment, can be effective in controlling breast cancer locally, with outcomes comparable to whole breast irradiation, while reducing treatment time and potentially unnecessary radiation exposure. ^{1 2 3 4 5}

Is accelerated partial breast irradiation (APBI) safe for breast cancer patients?

Accelerated partial breast irradiation (APBI) is generally considered safe for breast cancer patients, with studies showing it is well-tolerated and associated with manageable late toxicity, especially in older patients with low-risk breast cancer. ^{1 2 4 6 7}

How is the treatment Partial Breast Irradiation (PBI) different from other breast cancer treatments?

Partial Breast Irradiation (PBI) is unique because it targets only the part of the breast where cancer was removed, allowing for a shorter treatment time of 1 to 5 days compared to the 5-6 weeks required for whole-breast irradiation. This approach can reduce exposure to healthy tissue and may be more convenient for patients. ^{1 3 5 8 9}

What is the purpose of this trial?

In a small study at Johns Hopkins, women were treated with partial breast irradiation and chemotherapy given at the same time. We are now testing in a bigger study whether giving partial breast irradiation and chemotherapy at the same time (our new method) has the same side effects and outcomes as giving partial breast irradiation and chemotherapy at different times(older method). In this study women who had their breast cancer removed but need radiation to the breast will be randomized to partial breast irradiation at the same time as chemotherapy or partial breast radiation at a different time than chemotherapy. Randomization is like flipping a coin but in this study about 2 of every 3 women will get the new method.

Research Team

Richard Zellars, MD

Principal Investigator

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

Eligibility Criteria

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.

My breast cancer is either squamous cell or sarcoma.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Accelerated partial irradiation for breast cancer: systematic review and meta-analysis of 8653 women in eight randomized trials. [2022]

2. United States 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. [2018]

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

Accelerated partial breast irradiation: where do we stand? [2019]

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

Is oncoplastic surgery a contraindication for accelerated partial breast radiation using the interstitial multicatheter brachytherapy method? [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

A treatment planning study comparing whole breast radiation therapy against conformal, IMRT and tomotherapy for accelerated partial breast irradiation. [2007]

6. United States 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. [2021]

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

Accelerated Partial Breast Irradiation: Association of Dosimetric Parameters With Patient-Reported Outcomes. [2023]

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

Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: toxicity analysis of RTOG 95-17. [2022]

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

Breast conservation therapy utilizing partial breast brachytherapy for early-stage cancer of the breast: a retrospective review from the Saint Luke's Cancer Institute. [2015]