A Phase I Study of Rucaparib Administered Concurrently With Postoperative Radiotherapy in Patients With Triple Negative Breast Cancer With an Incomplete Pathologic Response Following Neoadjuvant Chemotherapy
Overview
- Phase
- Phase 1
- Intervention
- Rucaparib
- Conditions
- Breast Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 31
- Locations
- 8
- Primary Endpoint
- Dose Limiting Toxicities
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
The purpose of this study is to test the safety of a study drug called Rucaparib, administered in combination with the type of radiation therapy that is usually given to women with your form of breast cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female, ≥ 18 years of age.
- •Non-metastatic, histologically or cytologically-confirmed TNBC (defined as ER \<1%, PR \<1%, her-2-neu 0-1+ by IHC or FISH-negative or as per MD discretion), with evidence of residual disease in the breast or lymph nodes after neoadjuvant chemotherapy, at the time of definitive surgical treatment.
- •Non-metastatic, histologically or cytologically-confirmed hormone-receptor positive, Her2/neu negative breast cancer (defined as ER \>1% or PR \>1% AND Her-2/neu 0-1+ by IHC or FISH-negative, or as per MD discretion), with evidence of residual grade 3 invasive breast cancer AND either 1) \>5 cm of residual disease in the breast OR 2) ≥ 4 axillary LNs in the axilla after neoadjuvant chemotherapy, at the time of definitive surgical treatment.
- •Definitive surgical treatment with breast-conserving surgery or mastectomy and axillary lymph node evaluation.
- •At least 6-month life expectancy, ECOG Performance status \<
- •Willingness to discontinue any cytotoxic chemotherapeutic agents, and biologic therapy at least 2 weeks prior to the start of RT.
- •Adequate organ function (assessed within 30 days prior to initiation of protocol treatment, unless otherwise indicated) as follows:
- •Absolute Neutrophil Count (ANC) ≥1500/mm\^3
- •Platelet Count ≥100,000/mm\^3
- •Hemoglobin ≥9.0 g/dL (after transfusion if required) Renal Function
Exclusion Criteria
- •Gross residual tumor on imaging or positive margins after breast conserving surgery that are un-excised, as radiation dose in the study will be limited to 60 Gy.
- •Complete pathologic response to NAC.
- •Receipt of PARP inhibitor prior to RT.
- •Pregnant or expecting to conceive within the projected duration of the trial, starting with screening visit through 180 days after the last dose of trial treatment.
- •Prior history of radiation therapy to the ipsilateral breast and/or regional nodes is not allowed (prior RT to other sites is permitted).
- •Patients with breast augmentation implants are excluded.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to rucaparib.
- •Concomitant anti-neoplastic treatment is not allowed during protocol treatment and should be completed at least 2 weeks prior to commencement of protocol treatment, with resolution of associated acute toxicities. Bisphosphonates are permitted without restriction even during protocol treatment. Maintenance pembrolizumab is permitted during the protocol treatment.
- •Significant comorbidity: Patients with clinically significant and uncontrolled major disease or disorder that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit study compliance.
- •Ongoing therapy with other investigational agents. Patients may not be receiving any other investigational agents.
Arms & Interventions
Rucaparib Administered With Radiation
one dose level (200 mg BID, 200 mg QD, 300 mg BID, 300 mg QD or 400 mg BID) concurrently with a 6-week course of radiotherapy and 4 additional weeks of maintenance rucaparib at the same dose level. Radiotherapy will consist of 50 Gy in 2 Gy per fraction to the breast or chest wall with or without regional nodes plus a 10 Gy boost to the lumpectomy cavity, to a total dose of 60 Gy. A 10 Gy boost to the post-mastectomy scar is allowed at the discretion of the treating physician.
Intervention: Rucaparib
Rucaparib Administered With Radiation
one dose level (200 mg BID, 200 mg QD, 300 mg BID, 300 mg QD or 400 mg BID) concurrently with a 6-week course of radiotherapy and 4 additional weeks of maintenance rucaparib at the same dose level. Radiotherapy will consist of 50 Gy in 2 Gy per fraction to the breast or chest wall with or without regional nodes plus a 10 Gy boost to the lumpectomy cavity, to a total dose of 60 Gy. A 10 Gy boost to the post-mastectomy scar is allowed at the discretion of the treating physician.
Intervention: Radiotherapy
Outcomes
Primary Outcomes
Dose Limiting Toxicities
Time Frame: 1 year
Number of Dose Limiting Toxicities encountered at each dose level. The trial will be monitored using TITE-CRM. Assuming a model for the time to occurrence of toxic response as a function of dose, the method allows information from all enrolled patients to be used when allocating a new patient to a dose level.