Triple Negative Breast CancerPhase 2INTEGRALNCT04095689
Docetaxel Chemotherapy and Pembrolizumab Plus Interleukin-12 Gene Therapy in Triple Negative Breast Cancer
A Phase 2 study testing Docetaxel, Pembrolizumab and IL-12 gene therapy in people with Triple Negative Breast Cancer and Anthracycline-refractory TNBC, run by The Methodist Hospital Research Institute at 1 site in United States.
Trial summary
The purpose of this research study is to test the safety and effectiveness of docetaxel chemotherapy and pembrolizumab plus adenoviral-mediated interleukin-12 (ADV/IL-12) gene therapy in patients with anthracycline-refractory, triple negative breast cancer (TNBC). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Triple Negative Breast Cancer, Anthracycline-refractory TNBC
- What is being tested?
- Docetaxel, Pembrolizumab and IL-12 gene therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 12 May 2021to 3 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients are eligible to be included in the trial only if all of the following criteria apply:
- The patient (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Female ≥ 18 years of age on the day of informed consent signing.
- Histologically confirmed triple negative breast cancer is defined as estrogen receptor (ER), progesterone receptor (PR), and HER2 negative. ER/PR negativity is defined as <10% IHC staining of any intensity.
- HER2 negativity is defined as the following per the 2018 American Society of Clinical Oncology and College of American Pathologists guidelines.
- 4. Refractory to standard neoadjuvant anthracycline-containing chemotherapy regimen, demonstrated on MRI.
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- 5. Bilateral breast cancers that individually meet eligibility criteria are allowed.
- 6. Prior immunotherapy treatment allowed. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Adequate organ function as defined in Table 1. All screening labs should be performed within 28 days of trial treatment initiation.
- 9. Cardiac ejection fraction ≥45%. 10. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- A WOCBP who agrees to follow the contraceptive guidance in during the treatment period and for at least 120 days after the last dose of trial treatment. WOCBP must have a negative serum pregnancy test (β-human chorionic gonadotropin [β-HCG]) within 72 hours prior to trial treatment administration.
- 11. Willing to provide biopsy tissue as required by the trial. 12. Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits and examinations.
Who cannot join
- History of poorly controlled hypertension (defined as systolic blood pressure >150 mmHg). Patients whose hypertension has been well controlled on the same treatment for 1 year prior to Cycle 1, Day 1 are eligible. Only patients on single-agent antihypertensive therapy are allowed.
- History of New York Heart Association class III or greater cardiac disease.
- History of myocardial infarction, stroke, ventricular arrhythmia, or greater than first-degree conduction defect within the past 12 months.
- History of congenital QT prolongation.
- Absolute corrected QT interval of >480 msec in the presence of potassium >4.0 mEq/L and magnesium >1.8 mg/dL.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to trial treatment administration.
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- NOTE: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- 8. Concurrent use of any complementary or alternative medicines. 9. Concurrent use of inhibitors or inducers of cytochrome P450 (CYP)3A4 and CYP2D6 10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to trial treatment administration.
- 11. Known history of active tuberculosis (Bacillus Tuberculosis). 12. Known or suspected hypersensitivity to any component or excipient of the proposed regimen (docetaxel chemotherapy, gene vector, pembrolizumab).
- 13. Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 neuropathy may be eligible. If patient received major surgery, she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting the trial treatment.
- 14. Known additional malignancy that is progressing or requires active treatment. NOTE: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded.
- 15. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- 16. History of (noninfectious) pneumonitis that required steroids or current pneumonitis.
- 17. Active infection requiring systemic therapy. 18. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
- 19. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 20. Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the prescreening or screening visit through 120 days after the last dose of trial treatment.
- 21. Known history of human immunodeficiency virus (HIV). 22. Known history of hepatitis B (defined as hepatitis B surface antigen reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection.
- 23. Received a live vaccine within 30 days prior to trial treatment administration. 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, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Houston Methodist Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase II Study of Docetaxel Chemotherapy With Pembrolizumab and Interleukin-12 Gene Therapy in Patients With Anthracycline- Refractory Triple Negative Breast Cancer (INTEGRAL)
The purpose of this research study is to test the safety and effectiveness of docetaxel chemotherapy and pembrolizumab plus adenoviral-mediated interleukin-12 (ADV/IL-12) gene therapy in patients with anthracycline-refractory, triple negative breast cancer (TNBC).
Read the detailed description
The purpose of this study is to learn how triple negative breast cancer (TNBC) responds to the use of chemotherapy, pembrolizumab, and gene therapy together in patients who have previously not responded to treatment. We will also look at the effects, good or bad, the study therapy has on you and your TNBC.
Chemotherapy given before breast cancer surgery is called neoadjuvant chemotherapy. It shrinks the breast tumor, so it is easier to remove during surgery. Docetaxel is often used for the neoadjuvant treatment of breast cancer. Unfortunately, a lot of breast tumors do not shrink with docetaxel chemotherapy treatment. Docetaxel chemotherapy is standard care for TNBC.
Pembrolizumab is a type of treatment that stimulates your own immune system to attack cancer cells. Your immune system is normally your body's first defense against threats like cancer. However, sometimes cancer cells produce signals that prevent the immune system from detecting and killing them. Pembrolizumab helps your immune system so it can detect and attack cancer cells. Chemotherapy plus pembrolizumab has been shown to be better than chemotherapy alone for shrinking breast tumors before surgery.
To help increase the tumor-shrinking activity of docetaxel chemotherapy and pembrolizumab, you will be given more treatments, Interleukin-12 (IL-12) gene therapy This treatments will be used to boost the cancer-fighting ability of your immune system. Thus, the use of IL-12 gene therapy with docetaxel chemotherapy and pembrolizumab may make your immune system work harder to shrink your tumor. IL-12 is a substance that is normally made by certain immune cells in the body. IL-12 stimulates T cells, a special type of immune cell in the blood, to respond to threats to your body like cancer.
After you finish the study treatment, you will have your breast cancer surgery.
- Being tested
- Docetaxel, Pembrolizumab, IL-12 gene therapy
- Keywords
- triple negative breast cancer, neoadjuvant, pembrolizumab, anthracycline-refractory TNBC
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Also called Taxotere
Microtubule-targeting drug (inhibits microtubule depolymerization)
PembrolizumabDrug
Also called Keytruda
Programmed cell death-1 (PD-1) inhibitor
IL-12 gene therapyDrug
Adenoviral-mediated IL-12
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | docetaxel chemotherapy and pembrolizumab plus IL-12 gene therapy. Receives: Drug: Docetaxel; Drug: Pembrolizumab; Drug: IL-12 gene therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR) Rate of Docetaxel Chemotherapy and Pembrolizumab Plus IL-12 Gene Therapy
To determine the pCR rate of docetaxel chemotherapy and pembrolizumab plus IL-12 gene therapy in patients with TNBC per RECIST v1.1 assessed by CT Scan or MRI. CR: Disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter of target lesions, using the baseline sum longest diameter as a reference. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, using the smallest sum longest diameter as a reference. PD: At least a greater than or equal to 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Clinical PD: Patients who in the opinion of the treating PI have clinical evidence of PD may be classified as having PD
Measured: 18 weeks
Secondary outcomes (1)
Number of Participants With Treatment-related Adverse Events
To determine the number of participants with treatment-related adverse events, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2019
- Study start12 May 2021
- Primary completion3 Jun 2024
- Study completion3 Jun 2024
Why it stopped: Stopping rules met per protocol, trial will be terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Polly A. Niravath, MD, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04095689
- Sponsor's protocol ID
- PRO00028602
- Acronym
- INTEGRAL
- Status last verified
- Jan 2026
- First submitted
- 18 Sep 2019
- Last updated
- 23 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Docetaxel Chemotherapy With Pembrolizumab and Interleukin-12 Gene Therapy in Patients With Anthracycline- Refractory Triple Negative Breast Cancer (INTEGRAL)
- ClinicalTrials.gov ID
- NCT04095689
- Acronym / sponsor ID
- INTEGRAL / PRO00028602
- Keywords
- triple negative breast cancer, neoadjuvant, pembrolizumab, anthracycline-refractory TNBC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Stopping rules met per protocol, trial will be terminated
- Enrolment
- 8 participants (actual)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 12 May 2021 (actual)
- Primary completion
- 3 Jun 2024 (actual)
- Study completion
- 3 Jun 2024 (actual)
- First posted
- 19 Sep 2019 (actual)
- Results
- Posted 23 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to test the safety and effectiveness of docetaxel chemotherapy and pembrolizumab plus adenoviral-mediated interleukin-12 (ADV/IL-12) gene therapy in patients with anthracycline-refractory, triple negative breast cancer (TNBC).
Detailed description
The purpose of this study is to learn how triple negative breast cancer (TNBC) responds to the use of chemotherapy, pembrolizumab, and gene therapy together in patients who have previously not responded to treatment. We will also look at the effects, good or bad, the study therapy has on you and your TNBC.
Chemotherapy given before breast cancer surgery is called neoadjuvant chemotherapy. It shrinks the breast tumor, so it is easier to remove during surgery. Docetaxel is often used for the neoadjuvant treatment of breast cancer. Unfortunately, a lot of breast tumors do not shrink with docetaxel chemotherapy treatment. Docetaxel chemotherapy is standard care for TNBC.
Pembrolizumab is a type of treatment that stimulates your own immune system to attack cancer cells. Your immune system is normally your body's first defense against threats like cancer. However, sometimes cancer cells produce signals that prevent the immune system from detecting and killing them. Pembrolizumab helps your immune system so it can detect and attack cancer cells. Chemotherapy plus pembrolizumab has been shown to be better than chemotherapy alone for shrinking breast tumors before surgery.
To help increase the tumor-shrinking activity of docetaxel chemotherapy and pembrolizumab, you will be given more treatments, Interleukin-12 (IL-12) gene therapy This treatments will be used to boost the cancer-fighting ability of your immune system. Thus, the use of IL-12 gene therapy with docetaxel chemotherapy and pembrolizumab may make your immune system work harder to shrink your tumor. IL-12 is a substance that is normally made by certain immune cells in the body. IL-12 stimulates T cells, a special type of immune cell in the blood, to respond to threats to your body like cancer.
After you finish the study treatment, you will have your breast cancer surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Docetaxel, Drug: Pembrolizumab, Drug: IL-12 gene therapydocetaxel chemotherapy and pembrolizumab plus IL-12 gene therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients are eligible to be included in the trial only if all of the following criteria apply:
- The patient (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Female ≥ 18 years of age on the day of informed consent signing.
- Histologically confirmed triple negative breast cancer is defined as estrogen receptor (ER), progesterone receptor (PR), and HER2 negative. ER/PR negativity is defined as <10% IHC staining of any intensity.
- HER2 negativity is defined as the following per the 2018 American Society of Clinical Oncology and College of American Pathologists guidelines.
Key exclusion criteria (18 listed)
- NOTE: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- 8. Concurrent use of any complementary or alternative medicines. 9. Concurrent use of inhibitors or inducers of cytochrome P450 (CYP)3A4 and CYP2D6 10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to trial treatment administration.
- 11. Known history of active tuberculosis (Bacillus Tuberculosis). 12. Known or suspected hypersensitivity to any component or excipient of the proposed regimen (docetaxel chemotherapy, gene vector, pembrolizumab).
- 13. Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 neuropathy may be eligible. If patient received major surgery, she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting the trial treatment.
- 14. Known additional malignancy that is progressing or requires active treatment. NOTE: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DocetaxelAlso: TaxotereMicrotubule-targeting drug (inhibits microtubule depolymerization) | Drug | Experimental |
| PembrolizumabAlso: KeytrudaProgrammed cell death-1 (PD-1) inhibitor | Drug | Experimental |
| IL-12 gene therapyAdenoviral-mediated IL-12 | Drug | Experimental |
Primary outcome
Pathological Complete Response (pCR) Rate of Docetaxel Chemotherapy and Pembrolizumab Plus IL-12 Gene Therapy
Time frame: 18 weeks
To determine the pCR rate of docetaxel chemotherapy and pembrolizumab plus IL-12 gene therapy in patients with TNBC per RECIST v1.1 assessed by CT Scan or MRI. CR: Disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter of target lesions, using the baseline sum longest diameter as a reference. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, using the smallest sum longest diameter as a reference. PD: At least a greater than or equal to 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Clinical PD: Patients who in the opinion of the treating PI have clinical evidence of PD may be classified as having PD
1 secondary outcome
Number of Participants With Treatment-related Adverse Events
Time frame: 18 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel, Pembrolizumab and IL-12 gene therapy in people with Triple Negative Breast Cancer and Anthracycline-refractory TNBC, run by The Methodist Hospital Research Institute 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 12 inclusion and 18 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: stopped early, as of the sponsor's last update on 23 Jan 2026. 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?
Yes. Results are posted in the registry (first posted 23 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (pCR) Rate of Docetaxel Chemotherapy and Pembrolizumab Plus IL-12 Gene Therapy (time frame: 18 weeks). 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 23 Jan 2026.