A Study of Rucaparib Administered With Radiation in Patients With Triple Negative Breast Cancer With an Incomplete Response Following Chemotherapy

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Active, not recruiting; Phase 1

Conditions: Breast Cancer

Treatments: Radiation: Radiotherapy; Drug: Rucaparib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03542175

18-002

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 < 2.
• 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:

Hematology

• Absolute Neutrophil Count (ANC) ≥1500/mm^3

• Platelet Count ≥100,000/mm^3

• Hemoglobin ≥9.0 g/dL (after transfusion if required) Renal Function

• Creatinine Serum ≤ 1.5 mg/dL or Creatinine Clearance ≥ 45 mL/min^a Hepatic Function

• Bilirubin ≤ 1.5 mg/dL

• Aspartate Aminotransferase (AST) ≤ 2.5 x ULN^b

• Alanine Aminotransferase (ALT) ≤ 2.5 x ULN ULN = upper normal limit of institution's normal range

  1. If calculated creatinine clearance is < 45mL/min, a 24-hour urine collection for creatinine clearance may be performed

  2. Subjects with documented Gilbert's disease may have bilirubin up to 2.5 mg/dL

     • Negative serum pregnancy test within 14 days prior to study treatment if a woman has child-bearing potential. Subjects of child bearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
     • Ability to swallow and retain oral medications.
     • Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
     • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the duration of study participation. Should a woman become pregnant while participating on study, she should inform the treating physician immediately.

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.
• Unresolved toxicity from other agents. Patients with unresolved CTCAE v4.03 Grade 3 or greater toxicity from prior administration of another investigational drug and/or anti-cancer treatment are not eligible.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

31 participants in 1 patient group

Rucaparib Administered With Radiation

Experimental group

Description:

Treatment will consist of rucaparib at one dose level (300 mg BID, 400 mg BID, 500 mg BID or 600 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.

Treatment:

Radiation: Radiotherapy

Drug: Rucaparib