Metastatic Breast CancerPhase 2INDUCENCT06793553
Induction Therapy of PTX+BV Followed by Atezolizumab+Nab-PTX for PD-L1+ TNBC
A Phase 2 study testing Induction therapy in people with Metastatic Breast Cancer, run by Japan Breast Cancer Research Group at 1 site in Japan.
Trial summary
The objective of this research is to evaluate the efficacy of the treatment strategy to administer atezolizumab + nab-paclitaxel (PTX) following 2 cycles of induction therapy with PTX + bevacizumab (induction treatment strategy) in programmed cell death ligand-1 (PD-L1)-positive metastatic triple-negative breast… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Induction therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteJapan
- Study dates
- 13 Sep 2024to 30 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Diagnosed with metastatic recurrent or unresectable advanced TNBC
- Documented PD-L1 positivity (SP142 IC ≥ 1) confirmed by local assessment of the most recent tumor sample or an archival tumor sample.
- In the case of patients who were candidates for curative treatment, the duration from the completion of the curative treatment {date of surgery for primary breast cancer or date of last dose of peri-operative drug therapy (including anthracycline regimen, taxane regimen, anti-PD-(L)1 antibody, capecitabine, poly ADP-ribose polimerase [PARP] inhibitors, etc.), whichever is later} to the first local or distant recurrence should be at least 6 months. The date of postoperative radiotherapy is not included in this calculation. The use of anti-PD-(L)1 antibodies is allowed during perioperative drug therapy.
- ECOG PS 0-1
- Female or male aged 18 years or older.
- Histologically or cytologically confirmed TNBC that is ER-negative (< 10% positive cell occupancy or Allred Proportion score of 0-2), HER2-negative (IHC 1+ or less or FISH/DISH negative) according to ASCO/CAP Criteria 2018 (in the case of IHC2+, negativity is confirmed by FISH/DISH).
Show all 14Show fewer
- Patients who have not received chemotherapy for metastatic recurrent or unresectable advanced cancer. However, prior treatment with PARP inhibitors for metastatic recurrent or unresectable advanced cancers in patients with pathogenic BRCA variants is allowed.
- Having measurable or non-measurable lesions as assessed by local CT or MRI. Tumor lesions located at a previously irradiated site will be considered evaluable if unequivocal progression is seen after radiation.
- Laboratory tests performed within 14 days before enrollment meet the following criteria [1] to [8]. However, patients must not have received granulocyte colony-stimulating factor (G-CSF) or blood transfusion within 14 days prior to the date of blood sampling.
- [1] Neutrophil count ≥ 1500/mm3 [2] Platelet count ≥ 10 x 104/mm3 [3] Hemoglobin ≥ 8.0 g/dL [4] AST (GOT) ≤ 100 IU/L (≤ 200 IU/L if liver metastasis is present) [5] ALT (GPT) ≤ 100 IU/L(≤ 200 IU/L if liver metastasis is present) [6] Total bilirubin ≤ 1.5 mg/dL Total bilirubin < 3.0 mg/dL for patients with Gilbert's syndrome [7] Creatinine ≤ 1.5 mg/dL [8] Any of the following criteria is met: i) Urine protein (dipstick) is negative (-) or 1+ ii) If urine protein (dipstick) is ≥ 2+; Measurement of 24-hour urine protein shows urine protein ≤ 1 g/24 hours (may be substituted by urine protein/creatinine ratio ≤ 1)
- Blood pressure is sufficiently controlled (systolic blood pressure ≤ 150 mmHg and diastolic blood pressure ≤ 90 mmHg with ≤ 2 antihypertensive drugs [counted as the number of combinations]).
- Patients expected to survive for at least 3 months.
- Written consent has been obtained from the patient himself/herself after sufficient explanation of the contents of the study before registration.
- In the case of female patients of childbearing potential (including patients who have no menstruation for medical reasons such as chemical menopause), the patients must agree to continue to practice contraception until 5 months after the last dose of atezolizumab or 6 months after the last dose of bevacizumab, nab-PTX or PTX, whichever comes later. Patients must also agree not to breastfeed during study treatment and for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab. In the case of male patients with a partner of childbearing potential, the patient whose partner must agree to continue to practice contraception until 6 months after the last administration of PTX and nab-PTX.
Who cannot join
- Having active brain metastases or carcinomatous meningitis. Previously treated brain metastases are allowed if neurological symptoms have returned to baseline and are clinically stable for at least 2 weeks prior to enrollment.
- Patients with a history of invasive malignancy within 3 years prior to enrollment. However, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or lesions equivalent to carcinoma in situ or intramucosal carcinoma that are assessed as cured by local treatment are not included in active double cancer.
- Concurrent or metachronous bilateral invasive breast cancer. However, the patients will be accepted if bilateral lesions are TNBC and are confirmed to be PD-L1-positive by evaluation using a sample of a recurrent lesion.
- Patients who have received radiotherapy within 14 days prior to enrollment. (Administration or irradiation on the same day of the week 14 days prior to the day of enrollment is permitted.)
- Patients who have received other study drugs within 14 days prior to enrollment. (Administration on the same day of the week 14 days prior to the day of enrollment is permitted.)
- Administration of a live vaccine within 30 days of the first dose of the study drug. Administration of inactivated vaccines is permitted.
Show all 20Show fewer
- Patients who have received systemic corticosteroid or immunosuppressant equivalent to prednisone exceeding 10 mg/day within 14 days prior to enrollment for active autoimmune disease. (excluding temporary administration for examination or prophylactic administration)
- Active infection requiring systemic treatment.
- Patients who concurrently have interstitial lung disease/pneumonitis at the time of enrollment or who have a history of interstitial lung disease/pneumonitis requiring systemic corticosteroids administration. (A history of radiation pneumonitis [fibrosis] within the radiation field is permitted.)
- Patients who are pregnant, possibly pregnant, or lactating.
- Patients who are positive for HBs antigen or HCV antibody. Patients positive for HCV antibody whose HCV virus level is below the detection limit will be permitted.
- Patients who are positive for HIV-1 antibody or HIV-2 antibody (test is not essential for enrollment).
- Patients with significant cardiovascular disease. Patients with a history of myocardial infarction, acute coronary artery disease, coronary angioplasty/stenting/bypass grafting within the last 6 months. Patients with congestive heart failure of Class III to IV of the New York Heart Association.
- Patients with the following history/concomitant diseases:
- [1] Poorly controlled diabetes mellitus [2] Grade ≥ 2 peripheral sensory neuropathy [3] Congenital haemorrhagic diathesis/coagulopathy [4] Arterial thromboembolism (cerebral infarction, etc.) or venous thromboembolism (deep vein thrombosis, pulmonary embolism, etc.) within 6 months prior to enrollment [5] Gastrointestinal perforation, active gastrointestinal ulcer, and Grade ≥ 3 haemorrhage (site not specified) [6] Other serious complications (renal failure, hepatic failure, etc.)
- Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's completion of the study, or is not in the best interest of the participant to participate in.
- Patients with any psychiatric condition that may interfere with the conduct of the study.
- Patients with a history of hypersensitivity to the study drug or its analogues.
- Patients with alcohol intolerance or a history of hypersensitivity to Cremophor.
- Patients with a history of active tuberculosis infection.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Norikazu Masuda contact
Japan1 site, 1 recruiting
- Recruiting
Yukinori Ozaki
Koto-ku, 3-8-31, Tokyo, 135-8550
Yukinori Ozaki, +81-3-3520-0111, yukinori.ozaki@jfcr.or.jp
About this study
Official title: Randomized Phase II Trial Evaluating the Efficacy of Paclitaxel+Bevacizumab INDUCtion Followed by at atEzolizumab+Nab-paclitaxel for PD-L1-positive Metastatic Triple Negative Breast Cancer (JBCRG-M10, CMA-0196) (INDUCE Trial)
The objective of this research is to evaluate the efficacy of the treatment strategy to administer atezolizumab + nab-paclitaxel (PTX) following 2 cycles of induction therapy with PTX + bevacizumab (induction treatment strategy) in programmed cell death ligand-1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC) in comparison with the standard atezolizumab + nab-PTX therapy.
Read the detailed description
The objective of this research is to evaluate the efficacy of the treatment strategy to administer atezolizumab + nab-PTX following 2 cycles of induction therapy with PTX + bevacizumab (induction treatment strategy) in PD-L1-positive mTNBC in comparison with the standard atezolizumab + nab-PTX therapy in a rondomized phase II design.
It is hypothesized in this research that in patients with PD-L1-positive mTNBC, 2 cycles of PTX+ bevacizumab induction therapy induce early response and an immune microenvironment conducive to the benefits of immunotherapy, and improve progression-free survival as compared with the standard treatment with atezolizumab + nab-PTX therapy (standard treatment group). The primary objective of this research is to investigate this hypothesis.
A key secondary objective is to compare the 2-year PFS rate between the induction therapy group and the standard treatment group in order to assess the long-term effect of the induction treatment strategy. Furthermore, in patients in the induction therapy group who are not assessed as PD in the first imaging assessment, the 2-year PFS rate will be compared to the reference value expected in a historical control to examine the benefits of the induction therapy.
Other secondary objectives are to compare the response rate and the disease control rate as efficacy endpoints and to evaluate the effect of the induction treatment strategy on early PD. Overall survival (OS) will also be compared.
In addition, with the aim of exploring the mechanism by which the induction treatment strategy contributes to enhancement of the effect of the standard treatment with atezolizumab + nab-PTX therapy, the immune status in the tumor microenvironment and peripheral blood will be evaluated, and its relationship with antitumor effects will be investigated.
For evaluation of efficacy and safety in the induction therapy group, 2 cycles of induction therapy + immunochemotherapy will be evaluated as a series of treatments.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Induction therapy
- Keywords
- PD-L1-positive, bevacizumab, induction therapy, immunotherapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induction therapyDrug
2 cycles of PTX+ bevacizumab induction therapy followed by atezolizumab+nab-PTX
| Study group | Role | What they receive |
|---|---|---|
| Induction therapy group | Active comparator | 2 cycles of PTX + bevacizumab → atezolizumab + nab-PTX Receives: Drug: Induction therapy |
| Control group (standard treatment group) | Experimental | Atezolizumab + nab-PTX Receives: Drug: Induction therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) *
Whether the PFS is prolonged with statistical significance (level of significance, one-sided 10%) in the induction therapy group compared to the standard treatment group will be evaluated.
- In this research, all antitumor effects will be assessed based on the evaluation by the primary physician.
Measured: 2 years
Secondary outcomes (1)
(1) 2-year PFS rate (2) 2-year PFS rate in patients with non-PD on the first imaging assessment in the induction therapy group
The standard treatment group and the induction therapy group will be compared and evaluated.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2025
- Study start13 Sep 2024
- Primary completion31 Mar 2026 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Japan Breast Cancer Research Group
- Sponsor type
- University, hospital or other
- Collaborators
- Chugai Pharmaceutical
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06793553
- Sponsor's protocol ID
- JBCRG-M10
- Acronym
- INDUCE
- Status last verified
- Jan 2025
- First submitted
- 21 Jan 2025
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Ozaki Y, Koyama S, Morita S, Miyashita M, Tokuda E, Shimoi T, Fukuoka M, Masuda H, Takano Y, Shibata N, Yoshinami T, Murakami A, Tamaki K, Ishiguro H, Saji S, Miwa A, Matsunaga J, Zheng Y, Nishikawa H, Masuda N. Randomised, multicentre phase II study of bevacizumab and paclitaxel induction followed by atezolizumab and nab-paclitaxel in patients with PD-L1-positive metastatic triple-negative breast cancer: protocol for the INDUCE trial (JBCRG-M10). BMJ Open. 2026 May 13;16(5):e098088. doi: 10.1136/bmjopen-2024-098088.
PubMed 42128502
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Trial Evaluating the Efficacy of Paclitaxel+Bevacizumab INDUCtion Followed by at atEzolizumab+Nab-paclitaxel for PD-L1-positive Metastatic Triple Negative Breast Cancer (JBCRG-M10, CMA-0196) (INDUCE Trial)
- ClinicalTrials.gov ID
- NCT06793553
- Acronym / sponsor ID
- INDUCE / JBCRG-M10
- Conditions
- Metastatic Breast Cancer
- Keywords
- PD-L1-positive, bevacizumab, induction therapy, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 106 participants (estimated)
- Lead sponsor
- Japan Breast Cancer Research GroupUniversity, hospital or other
- Collaborators
- Chugai Pharmaceutical
- Study start
- 13 Sep 2024 (actual)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 27 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this research is to evaluate the efficacy of the treatment strategy to administer atezolizumab + nab-paclitaxel (PTX) following 2 cycles of induction therapy with PTX + bevacizumab (induction treatment strategy) in programmed cell death ligand-1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC) in comparison with the standard atezolizumab + nab-PTX therapy.
Detailed description
The objective of this research is to evaluate the efficacy of the treatment strategy to administer atezolizumab + nab-PTX following 2 cycles of induction therapy with PTX + bevacizumab (induction treatment strategy) in PD-L1-positive mTNBC in comparison with the standard atezolizumab + nab-PTX therapy in a rondomized phase II design.
It is hypothesized in this research that in patients with PD-L1-positive mTNBC, 2 cycles of PTX+ bevacizumab induction therapy induce early response and an immune microenvironment conducive to the benefits of immunotherapy, and improve progression-free survival as compared with the standard treatment with atezolizumab + nab-PTX therapy (standard treatment group). The primary objective of this research is to investigate this hypothesis.
A key secondary objective is to compare the 2-year PFS rate between the induction therapy group and the standard treatment group in order to assess the long-term effect of the induction treatment strategy. Furthermore, in patients in the induction therapy group who are not assessed as PD in the first imaging assessment, the 2-year PFS rate will be compared to the reference value expected in a historical control to examine the benefits of the induction therapy.
Other secondary objectives are to compare the response rate and the disease control rate as efficacy endpoints and to evaluate the effect of the induction treatment strategy on early PD. Overall survival (OS) will also be compared.
In addition, with the aim of exploring the mechanism by which the induction treatment strategy contributes to enhancement of the effect of the standard treatment with atezolizumab + nab-PTX therapy, the immune status in the tumor microenvironment and peripheral blood will be evaluated, and its relationship with antitumor effects will be investigated.
For evaluation of efficacy and safety in the induction therapy group, 2 cycles of induction therapy + immunochemotherapy will be evaluated as a series of treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Induction therapy group | Active comparator | Drug: Induction therapy2 cycles of PTX + bevacizumab → atezolizumab + nab-PTX |
| Control group (standard treatment group) | Experimental | Drug: Induction therapyAtezolizumab + nab-PTX |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Diagnosed with metastatic recurrent or unresectable advanced TNBC
- Documented PD-L1 positivity (SP142 IC ≥ 1) confirmed by local assessment of the most recent tumor sample or an archival tumor sample.
- In the case of patients who were candidates for curative treatment, the duration from the completion of the curative treatment {date of surgery for primary breast cancer or date of last dose of peri-operative drug therapy (including anthracycline regimen, taxane regimen, anti-PD-(L)1 antibody, capecitabine, poly ADP-ribose polimerase [PARP] inhibitors, etc.), whichever is later} to the first local or distant recurrence should be at least 6 months. The date of postoperative radiotherapy is not included in this calculation. The use of anti-PD-(L)1 antibodies is allowed during perioperative drug therapy.
- ECOG PS 0-1
- Female or male aged 18 years or older.
Key exclusion criteria (20 listed)
- Having active brain metastases or carcinomatous meningitis. Previously treated brain metastases are allowed if neurological symptoms have returned to baseline and are clinically stable for at least 2 weeks prior to enrollment.
- Patients with a history of invasive malignancy within 3 years prior to enrollment. However, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or lesions equivalent to carcinoma in situ or intramucosal carcinoma that are assessed as cured by local treatment are not included in active double cancer.
- Concurrent or metachronous bilateral invasive breast cancer. However, the patients will be accepted if bilateral lesions are TNBC and are confirmed to be PD-L1-positive by evaluation using a sample of a recurrent lesion.
- Patients who have received radiotherapy within 14 days prior to enrollment. (Administration or irradiation on the same day of the week 14 days prior to the day of enrollment is permitted.)
- Patients who have received other study drugs within 14 days prior to enrollment. (Administration on the same day of the week 14 days prior to the day of enrollment is permitted.)
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 |
|---|---|---|
| Induction therapy2 cycles of PTX+ bevacizumab induction therapy followed by atezolizumab+nab-PTX | Drug | Control group (standard treatment group), Induction therapy group |
Primary outcome
Progression-free survival (PFS) *
Time frame: 2 years
Whether the PFS is prolonged with statistical significance (level of significance, one-sided 10%) in the induction therapy group compared to the standard treatment group will be evaluated. * In this research, all antitumor effects will be assessed based on the evaluation by the primary physician.
1 secondary outcome
(1) 2-year PFS rate (2) 2-year PFS rate in patients with non-PD on the first imaging assessment in the induction therapy group
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Derived from this study: PubMed 42128502Ozaki Y, Koyama S, Morita S, Miyashita M, Tokuda E, Shimoi T, Fukuoka M, Masuda H, Takano Y, Shibata N, Yoshinami T, Murakami A, Tamaki K, Ishiguro H, Saji S, Miwa A, Matsunaga J, Zheng Y, Nishikawa H, Masuda N. Randomised, multicentre phase II study of bevacizumab and paclitaxel induction followed by atezolizumab and nab-paclitaxel in patients with PD-L1-positive metastatic triple-negative breast cancer: protocol for the INDUCE trial (JBCRG-M10). BMJ Open. 2026 May 13;16(5):e098088. doi: 10.1136/bmjopen-2024-098088.
- Individual participant dataSharing planned: Undecided
Related trials for Metastatic Breast Cancer
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingPhase 1/2
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Metastatic Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
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.
Norikazu Masuda contact
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 Induction therapy in people with Metastatic Breast Cancer, run by Japan Breast Cancer Research Group at 1 site in Japan.
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 14 inclusion and 20 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: looking for participants now, as of the sponsor's last update on 30 Jan 2025. 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 Japan. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yukinori Ozaki (+81-3-3520-0111, yukinori.ozaki@jfcr.or.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) * (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06793553, which also lists 1 linked publication.
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 30 Jan 2025.