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Breast CancerPhase 2PANDoRANCT03872505

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

A Phase 2 study testing Durvalumab, Radiation Therapy and Carboplatin in people with Breast Cancer and Triple Negative Breast Cancer, run by Cedars-Sinai Medical Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Triple Negative Breast Cancer
What is being tested?
Durvalumab, Radiation Therapy and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Jul 2022to Jul 2027
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • Not a woman of childbearing potential (WOCBP) as defined in Appendix C OR
  • A WOCBP who agrees to follow the contraceptive guidance in Appendix C during the treatment period and for at least 6 months after the last dose of study treatment.

Who cannot join

  • 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.
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  • 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
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • History of active primary immunodeficiency.
  • Known active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B, hepatitis C, or human immunodeficiency virus . Patients with a past or resolved HBV infection are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
  • Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
  • Stage IV (metastatic) breast cancer
  • Inflammatory breast cancer

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

Other trials in United States

About this study

Official title: A Randomized Phase II Study Evaluating Pathologic Response Rates Following Pre-operAtive Non-Anthracycline Chemotherapy, Durvalumab (MEDI4736) +/- RAdiation Therapy (RT) in Triple Negative Breast Cancer (TNBC): The PANDoRA Study.

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.

Being tested
Durvalumab, Radiation Therapy, Carboplatin, Paclitaxel
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
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabDrug

    Also called Imfimzi

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

  • Radiation TherapyRadiation

    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.

  • CarboplatinDrug

    IV administration weekly for 12 weeks

  • PaclitaxelDrug

    IV administration every week for 12 weeks

Study groups in NCT03872505
Study groupRoleWhat they receive
Chemotherapy + DurvalumabActive comparatorArm A: Carboplatin, Paclitaxel and Durvalumab
Receives: Drug: Durvalumab; Drug: Carboplatin; Drug: Paclitaxel
Chemo + Durvalumab + Radiation TherapyExperimentalArm B: Carboplatin, Paclitaxel and Durvalumab + Radiation Therapy
Receives: Drug: Durvalumab; Radiation: Radiation Therapy; Drug: Carboplatin; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 20 weeks from randomization

Secondary outcomes (8)
  1. Pathological complete invasive and in situ response rate (breast and axilla)

    Proportion of subjects without residual invasive and in situ cancer in the breast and axilla disease from randomization to definitive surgery.

    • Residual invasive cancer and in situ disease defined based on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by pathological assessment.

    Measured: 20 weeks from randomization

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

    Proportion of subjects without residual invasive cancer in the breast from randomization to definitive surgery.

    • Residual invasive breast cancer defined based on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant systemic therapy by pathological assessment.

    Measured: 20 weeks from randomization

  3. Residual Cancer Burden (RCB)

    Proportion of subjects with RCB 0-I, II or III from randomization to definitive surgery.

    -Residual Cancer Burden defined based on the RCB index, a component of four pathological parameters: bi-dimensional diameter of primary tumor bed, percent of cellularity in the tumor bed, number of involved lymph nodes and size of the largest nodal metastasis. The RCB possible scores are: RCB 0 (pCR), RCB I, RCB II, RCB III.

    Measured: 20 weeks from randomization

  4. Event Free Survival

    Mean difference in time (in months) from randomization to any of the following events progression of disease that precludes surgery, local or distant recurrence, or death due to any cause.

    Measured: 36 months from randomization

  5. Invasive disease-free survival (IDFS)

    Mean difference in time (in months) from date of surgery (date of no disease) to the first documentation of invasive progressive disease or death.

    Measured: 33 months from surgery

  6. Overall survival

    Mean difference in time (in months) from randomization to death.

    Measured: 36 months from randomization

  7. Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Incidence and severity of adverse events (AE) and serious adverse events (SAE) from cycle 1 day 1 until 30 days post-surgery.

    -AEs and SAEs based on CTCAE 5.0

    Measured: 24 weeks from treatment initiation

  8. Frequency of adjuvant treatment after surgery

    Average number of subjects receiving adjuvant treatment after surgery.

    Measured: 36 months from randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2019
  2. Study startJul 2022 (estimated)
  3. Primary completionJul 2022 (estimated)
  4. Study completionJul 2027 (estimated)

Why it stopped: lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03872505
Sponsor's protocol ID
IIT2018-17-McArthur-TCDRT
Acronym
PANDoRA
Status last verified
Aug 2021
First submitted
11 Mar 2019
Last updated
25 Aug 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab, Radiation Therapy and Carboplatin in people with Breast Cancer and Triple Negative Breast Cancer, run by Cedars-Sinai Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response rate in the breast and axilla (time frame: 20 weeks from randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.

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