Pre-operAtive Non-Anthracycline Chemotherapy, Durvalumab +/- RAdiation Therapy in Triple Negative Breast Cancer

NCT03872505 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: IIT2018-17-McArthur-TCDRT
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II randomized trial is for patients with clinical stage II-III, ER and PR \<10%, HER2-negative invasive breast carcinoma (triple negative breast cancer) for whom adjuvant RT is planned and pre-operative RT is deemed feasible by the treating radiation oncologist. Subjects will be randomized into arm A or B and treatment will last for 16 weeks. Both groups will receive Durvalumab 750mg IV Q2 weeks x 2 then a biopsy prior to durvalumab 1500mg IV Q4 weeks x 3 with paclitaxel and carboplatin IV weekly x 12. Arm B will receive radiation (24 Gy total) starting with the second durvalumab dose every other day (8Gy per fraction) for one week. Following treatment, subjects will receive SOC breast surgery and continue on to physician's choices SOC treatment during the 3 year follow up period. This study hopes to explore the impact of checkpoint blockade administration with a non- anthracycline chemotherapy regimen plus RT on post-surgery pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0) following 12 weeks of treatment and surgery.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Keywords

breast cancer; durvalumab; immunotherapy; triple negative; HER2 negative; ER/PR negative; carboplatin; radiation therapy; paclitaxel; neoadjuvant; stage II breast cancer; stage III breast cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate in the breast and axilla

  Proportion of subjects without residual invasive cancer in the breast and axilla from randomization to definitive surgery. Measured as the lack of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy at the time of definitive surgery.

  20 weeks from randomization

Secondary Outcomes (8)

• Pathological complete invasive and in situ response rate (breast and axilla)

  20 weeks from randomization

• Proportion of subjects with pathological invasive complete response in the breast only

  20 weeks from randomization

• Residual Cancer Burden (RCB)

  20 weeks from randomization

• Event Free Survival

  36 months from randomization

• Invasive disease-free survival (IDFS)

  33 months from surgery

Study Arms (2)

Chemotherapy + Durvalumab

ACTIVE COMPARATOR

Arm A: Carboplatin, Paclitaxel and Durvalumab

Drug: Durvalumab; Drug: Carboplatin; Drug: Paclitaxel

Chemo + Durvalumab + Radiation Therapy

EXPERIMENTAL

Arm B: Carboplatin, Paclitaxel and Durvalumab + Radiation Therapy

Drug: Durvalumab; Radiation: Radiation Therapy; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Durvalumab DRUG

IV administration of 5 treatments;every 2 weeks for 2 treatments and then every 4 weeks for 3 treatments

Also known as: Imfimzi

Chemo + Durvalumab + Radiation Therapy; Chemotherapy + Durvalumab

Radiation Therapy RADIATION

The second dose of durvalumab will be given in conjunction with an RT boost, consisting of 8 Gy in 3 fractions for a total of 24 Gy.

Chemo + Durvalumab + Radiation Therapy

Carboplatin DRUG

IV administration weekly for 12 weeks

Chemo + Durvalumab + Radiation Therapy; Chemotherapy + Durvalumab

Paclitaxel DRUG

IV administration every week for 12 weeks

Chemo + Durvalumab + Radiation Therapy; Chemotherapy + Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female patients with histologically confirmed invasive breast cancer, ER \<10%, PR \<10% and HER2-negative for whom adjuvant RT is planned and in whom pre-operative RT is feasible.
• Clinical stage II-III by the AJCC 8th definition, any nodal status (cT2-4N0 or cT1-4N1-3), biopsies of clinically suspicious lymph nodes to confirm nodal status is encouraged.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• At least 18 years of age on the day of signing informed consent.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Body weight \>30kg.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Patients with multifocal, multicentric or bilateral breast cancer are permitted if all suspicious foci have been biopsied and deemed "triple negative" per criterion 1.
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix C of this protocol during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant (see Appendix C), not breastfeeding, and at least one of the following conditions applies:

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization (see Appendix C). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure within 28 days prior to the first dose of study drug.
• History of allogenic organ transplantation.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
• Participation in another clinical study with an investigational product during the last 4 weeks, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• AstraZeneca: collaborator

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

durvalumab; Radiotherapy; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Heather McArthur, MD, MPH

  Cedars-Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 13, 2019
• Study Start: July 1, 2022
• Primary Completion: July 1, 2022
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 25, 2021

Record last verified: 2021-08

Locations

US (1)