Breast CancerPhase 2NCT00499122
NOV-002, Doxorubicin, Cyclophosphamide, and Docetaxel in Women With Newly Diagnosed Stage II or IIIC Breast Cancer
A Phase 2 study testing Cyclophosphamide, Docetaxel and Doxorubicin in people with Breast Cancer, run by University of Miami at 2 sites in United States.
Trial summary
RATIONALE: Oxidized glutathione (NOV-002) may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from… Read more about this study
- Who is it for?
- Ages 18 to 120 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Cyclophosphamide, Docetaxel and Doxorubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Jun 2007to Apr 2011
- 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 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Females age 18 years or older.
- The ability to provide written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time.
- Histologically confirmed infiltrating (invasive) breast cancer by core needle biopsy, with no evidence of metastatic disease except to the ipsilateral axillary lymph nodes.
- Clinical stage IIB - IIIC (T2-4, N0 or N1, M0 or - any T, N1-3, M0) breast cancer. The primary tumor must be greater than or equal to 2 cm (T2-4) or with pathologically proven axillary nodal involvement (N1-3).
- Patients with inflammatory breast cancer (T4) are permitted into the study.
- Clinically palpable tumor that meets the criteria of RECIST for palpable measurable disease. The primary tumor must be greater than or equal to 2 cm (T2-4) or with pathologically proven axillary nodal involvement (N1-3). Bilateral synchronic breast cancers are allowed but one of the primary tumors should be selected as the target tumor.
Show all 12Show fewer
- Primary tumor may be estrogen or progesterone receptor negative or positive, and human epidermal growth factor receptor 2 (HER-2/neu) negative as determined by either Fluorescent In Situ Hybridization (FISH) or 0-2+ staining by immunohistochemistry (IHC) (Hercept™).
- Normal cardiac ejection fraction (EF ≥ 50%) as determined by screening multigated acquisition scan (MUGA) or echocardiogram.
- No prior history of myocardial infarction, congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmias.
- Patients must be ambulatory with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- The patient or her caregiver must be able to self administer daily subcutaneous injections.
- Life expectancy greater than 6 months.
Who cannot join
- Prior therapy of any modality for the treatment of breast cancer
- Any prior therapy with an anthracycline or a taxane for any other indication
- HER-2 positive breast cancer defined as either gene amplification by Fluorescent In Situ Hybridization (FISH) or 3+ staining by IHC (Hercept™).
- Women who have a positive pregnancy test, no pregnancy test available, who are pregnant or who are lactating.
- Women of childbearing potential must agree to use a reliable and appropriate contraceptive method, which could include a double barrier method (condom plus diaphragm), an intrauterine device or oral contraceptives. Women with ER or PR positive breast cancer, should not, however, use oral contraceptives as a method of contraception. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Women with breast cancer that do not have palpable breast tumors at screening.
Show all 19Show fewer
- History of another malignancy within the last 5 years except curatively treated basal cell carcinoma of the skin or cervical intraepithelial neoplasia.
- Clinically significant (i.e. active) cardiac disease (NYHA Grade II or greater congestive heart failure, symptomatic coronary artery disease, unstable angina, and cardiac arrhythmia not well-controlled with medication), myocardial infarction within the last 6 months prior to study start, or screening ejection fraction of < 50%.
- Any of the following abnormal laboratory values:
- Absolute neutrophil count < 1.5 x 109/L
- Platelet count < 100 x 109/L
- Serum bilirubin > 1.5 x upper limit of normal (ULN)
- Serum alanine transaminase (ALT), aspartate transaminase (AST) > 2.5 x ULN
- Serum creatinine > 2.0 mg/dL or 177mmol/L or calculated creatinine clearance by the method of Cockcroft and Gault < 50mL/min).
- Any severe or poorly controlled systemic disease (e.g., hypertension; clinically significant cardiovascular, pulmonary, or metabolic disease, disorders of wound-healing, ulcer or bone fracture).
- Patients who have received any investigational treatment within 4 weeks of study start.
- Known infection with HIV, Hepatitis B virus (HBV), or Hepatitis C virus (HCV).
- Known hypersensitivity to any of the components of NOV-002 or to any of the study drugs.
- Patients assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, 29425
University of Miami
Miami, Florida, 33136
About this study
Official title: Phase II Study of Neoadjuvant Treatment With NOV-002 in Combination With Doxorubicin and Cyclophosphamide Followed by Docetaxel in Patients With Stages IIB-IIIC Breast Cancer
RATIONALE: Oxidized glutathione (NOV-002) may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving NOV-002 together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying how well giving oxidized glutathione (NOV-002) together with doxorubicin and cyclophosphamide followed by docetaxel works in treating women with newly diagnosed stage II or stage III breast cancer.
Read the detailed description
OUTLINE: This is a multicenter study.
Patients receive oxidized glutathione (NOV-002) IV twice on day -1 of course 1 and once on day 1 of courses 2-8. Patients receive NOV-002 subcutaneously once daily on days 2-21 of courses 1-8. Patients also receive chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 of courses 1-4 followed by docetaxel IV on day 1 of courses 5-8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Patients undergo definitive surgery 3-6 weeks after completion of neoadjuvant therapy.
Blood samples are obtained at baseline and periodically during study to measure serum and plasma protein glutathionlylation. Additional blood samples are collected from some patients for immunological correlative studies.
After completion of study therapy, patients are followed at 30 days.
- Conditions
- Breast Cancer
- Being tested
- Cyclophosphamide, Docetaxel, Doxorubicin, NOV 002
- Keywords
- stage II breast cancer, stage IIIC breast cancer, inflammatory breast cancer
- Medical subject headings
- Breast Neoplasms, Inflammatory Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called Cytoxan
DocetaxelDrug
Also called Cytoxan
DoxorubicinDrug
Also called Adriamycin
NOV 002Drug
Also called Oxidized glutathione
| Study group | Role | What they receive |
|---|---|---|
| NOV-002 and Chemotherapy | Experimental | * NOV-002:
* Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart
* Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration
* Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections
* Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1
* Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1
* Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1 Receives: Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: NOV 002 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Pathologic Complete Response in the Affected Breast After Protocol Therapy
The primary objective of this study is to define the rate of pathologic complete response rate (pCR) in the affected breast after the preoperative administration of NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with stage IIB-IIIC breast cancer. Pathologic complete response (pCR) is defined according to Hankoop et al [41] as either: the absence of any histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast or the presence of invasive tumor equal to or less than 10mm after preoperative treatment, determined at definitive breast surgery.
Measured: About 7 months
Secondary outcomes (2)
Definition of the Safety Profiles of Protocol Therapy
Definition of the safety profiles of protocol therapy in study participants as shown by the number of study participants experiencing adverse events or other toxicity.
Measured: Up to 30 days Post-Last Dose of Protocol Therapy, About 7 months
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders
The investigators hypothesized that patients with favorable responses, i.e. pCR, are more likely to have significantly lower levels of MDSCs than non-responders. MDSC levels will be measured at baseline and on day 1 of each treatment cycle, cycles 1 through 8.
Measured: Baseline, Day 1 of Cycles 1 through 8, about 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2007 (estimated)
- Study start4 Jun 2007
- Primary completionApr 2011
- Study completionApr 2011
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of MiamiThe 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
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Keisuke Shirai, MD, Study chair, Medical University of South CarolinaAlberto Montero, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499122
- Sponsor's protocol ID
- 20071167
- Other IDs
- MUSC-101072, MUSC-HR-17111
- Status last verified
- Dec 2017
- First submitted
- 10 Jul 2007
- Last updated
- 2 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Montero AJ, Diaz-Montero CM, Deutsch YE, Hurley J, Koniaris LG, Rumboldt T, Yasir S, Jorda M, Garret-Mayer E, Avisar E, Slingerland J, Silva O, Welsh C, Schuhwerk K, Seo P, Pegram MD, Gluck S. Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer. Breast Cancer Res Treat. 2012 Feb;132(1):215-23. doi: 10.1007/s10549-011-1889-0. Epub 2011 Dec 3.
PubMed 22138748
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Neoadjuvant Treatment With NOV-002 in Combination With Doxorubicin and Cyclophosphamide Followed by Docetaxel in Patients With Stages IIB-IIIC Breast Cancer
- ClinicalTrials.gov ID
- NCT00499122
- Acronym / sponsor ID
- 20071167
- Conditions
- Breast Cancer
- Keywords
- stage II breast cancer, stage IIIC breast cancer, inflammatory breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- 4 Jun 2007 (actual)
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 11 Jul 2007 (estimated)
- Results
- Posted 29 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Oxidized glutathione (NOV-002) may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving NOV-002 together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying how well giving oxidized glutathione (NOV-002) together with doxorubicin and cyclophosphamide followed by docetaxel works in treating women with newly diagnosed stage II or stage III breast cancer.
Detailed description
OUTLINE: This is a multicenter study.
Patients receive oxidized glutathione (NOV-002) IV twice on day -1 of course 1 and once on day 1 of courses 2-8. Patients receive NOV-002 subcutaneously once daily on days 2-21 of courses 1-8. Patients also receive chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 of courses 1-4 followed by docetaxel IV on day 1 of courses 5-8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Patients undergo definitive surgery 3-6 weeks after completion of neoadjuvant therapy.
Blood samples are obtained at baseline and periodically during study to measure serum and plasma protein glutathionlylation. Additional blood samples are collected from some patients for immunological correlative studies.
After completion of study therapy, patients are followed at 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NOV-002 and Chemotherapy | Experimental | Drug: Cyclophosphamide, Drug: Docetaxel, Drug: Doxorubicin, Drug: NOV 002* NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1 |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Females age 18 years or older.
- The ability to provide written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time.
- Histologically confirmed infiltrating (invasive) breast cancer by core needle biopsy, with no evidence of metastatic disease except to the ipsilateral axillary lymph nodes.
- Clinical stage IIB - IIIC (T2-4, N0 or N1, M0 or - any T, N1-3, M0) breast cancer. The primary tumor must be greater than or equal to 2 cm (T2-4) or with pathologically proven axillary nodal involvement (N1-3).
- Patients with inflammatory breast cancer (T4) are permitted into the study.
Key exclusion criteria (19 listed)
- Prior therapy of any modality for the treatment of breast cancer
- Any prior therapy with an anthracycline or a taxane for any other indication
- HER-2 positive breast cancer defined as either gene amplification by Fluorescent In Situ Hybridization (FISH) or 3+ staining by IHC (Hercept™).
- Women who have a positive pregnancy test, no pregnancy test available, who are pregnant or who are lactating.
- Women of childbearing potential must agree to use a reliable and appropriate contraceptive method, which could include a double barrier method (condom plus diaphragm), an intrauterine device or oral contraceptives. Women with ER or PR positive breast cancer, should not, however, use oral contraceptives as a method of contraception. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
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 |
|---|---|---|
| CyclophosphamideAlso: Cytoxan | Drug | NOV-002 and Chemotherapy |
| DocetaxelAlso: Cytoxan | Drug | NOV-002 and Chemotherapy |
| DoxorubicinAlso: Adriamycin | Drug | NOV-002 and Chemotherapy |
| NOV 002Also: Oxidized glutathione | Drug | NOV-002 and Chemotherapy |
Primary outcome
Rate of Pathologic Complete Response in the Affected Breast After Protocol Therapy
Time frame: About 7 months
The primary objective of this study is to define the rate of pathologic complete response rate (pCR) in the affected breast after the preoperative administration of NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with stage IIB-IIIC breast cancer. Pathologic complete response (pCR) is defined according to Hankoop et al [41] as either: the absence of any histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast or the presence of invasive tumor equal to or less than 10mm after preoperative treatment, determined at definitive breast surgery.
2 secondary outcomes
Definition of the Safety Profiles of Protocol Therapy
Time frame: Up to 30 days Post-Last Dose of Protocol Therapy, About 7 months
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders
Time frame: Baseline, Day 1 of Cycles 1 through 8, about 7 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22138748Montero AJ, Diaz-Montero CM, Deutsch YE, Hurley J, Koniaris LG, Rumboldt T, Yasir S, Jorda M, Garret-Mayer E, Avisar E, Slingerland J, Silva O, Welsh C, Schuhwerk K, Seo P, Pegram MD, Gluck S. Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer. Breast Cancer Res Treat. 2012 Feb;132(1):215-23. doi: 10.1007/s10549-011-1889-0. Epub 2011 Dec 3.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
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.
Keisuke Shirai, MD study chair
Medical University of South Carolina
Alberto Montero, MD principal investigator
University of Miami
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyclophosphamide, Docetaxel and Doxorubicin in people with Breast Cancer, run by University of Miami at 2 sites 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 19 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: finished, as of the sponsor's last update on 2 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 29 Mar 2013). 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?
Rate of Pathologic Complete Response in the Affected Breast After Protocol Therapy (time frame: About 7 months). 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 NCT00499122, 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 2 Jan 2018.