Breast CancerPhase 1/2NCT00834678
Bendamustine and Erlotinib in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Breast Cancer
A Phase 1/2 study testing bendamustine, erlotinib and Maintenance erlotinib in people with Breast Cancer, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as bendamustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- bendamustine, erlotinib and Maintenance erlotinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to Sep 2014
- Phase
- Phase 1/2
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed breast cancer meeting 1 of the following criteria:
- Unresectable stage IIIB or IIIC disease
- Stage IV disease
- Must be negative for all of the following:
- Estrogen receptor (< 10%)
- Progesterone receptor (<10%)
- HER-2 (negative FISH, IHC 0 - 1+, or IHC +2 with negative FISH)
- Measurable or evaluable disease
- No symptomatic or progressive CNS (central nervous system) metastases
- Previously treated CNS metastases allowed provided all of the following criteria are met:
- At least 8 weeks since prior radiation to brain or CNS metastases
- No concurrent steroids
- No leptomeningeal disease
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- Life expectancy ≥ 6 months
- WBC > 1,500/mm³
- Platelet count > 100,000/mm³
- Creatinine clearance > 40 mL/min
- Normal electrolytes (i.e., Na, K, and Ca normal; minor deviations are allowed if they do not impact on patient safety in the clinical judgment of the treating physician)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN in the presence of documented liver metastases)
- Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver or bone metastases)
- Not pregnant or nursing
- Fertile patients must use effective barrier contraception
- No uncontrolled intercurrent illness
- No active infection requiring systemic therapy
- Able to swallow oral medications and with no medical problems or prior surgeries that may interfere with the absorption of oral medications including the following:
- Uncontrolled nausea, vomiting, or diarrhea
- Lack of the physical integrity of the upper gastrointestinal tract
- Malabsorption syndrome
- No known hypersensitivity to bendamustine hydrochloride, mannitol, or erlotinib hydrochloride
- No prior malignancy in the past 5 years except for adequately treated basal cell or squamous cell skin carcinoma, or adequately treated stage I-II cancer for which the patient is in complete remission
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior adjuvant or neoadjuvant chemotherapy and 1 prior chemotherapy regimen in the metastatic setting allowed provided recovered from all acute toxicities
- No prior bendamustine hydrochloride or EGFR-directed therapy
- No other concurrent antineoplastic treatments, including radiotherapy, chemotherapy, biological therapy, hormonal therapy, immunotherapy, gene therapy, and surgery
- Intravenous bisphosphonates allowed
- No concurrent antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer
RATIONALE: Drugs used in chemotherapy, such as bendamustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving bendamustine together with erlotinib may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving bendamustine together with erlotinib in treating patients with stage IIIB, stage IIIC, or stage IV breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine the phase II dose and assess the toxicity of bendamustine hydrochloride and erlotinib hydrochloride in patients with triple-receptor (estrogen receptor, progesterone receptor, and HER-2)-negative, stage IIIB, IIIC, or IV breast cancer. (Phase I)
- To determine the efficacy of this regimen in these patients. (Phase II)
Secondary (Correlative)
- To assess the correlation between tumor EGFR expression and EGFR gene amplification and treatment efficacy and toxicity.
- To assess for differences in treatment efficacy between basal-like and non-basal-like cancers.
- To assess for differences in treatment efficacy between tumors with and without expression of DNA damage-response (DDR) checkpoint proteins.
- To assess for differences in the activation state of DDR checkpoint proteins based on breast cancer subtype.
OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study.
Patients receive bendamustine hydrochloride IV over 30 minutes on days 1-2 and oral erlotinib hydrochloride once daily on days 5-21. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Patients with no evidence of disease progression may continue with daily single-agent oral erlotinib hydrochloride on days 1-28. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.
Breast cancer tissue blocks from prior procedures are obtained for correlative studies. After a tissue microarray (TMA) and a TMA map are prepared, TMA slides are used for hematoxylin and eosin (H\&E) staining, FISH, and IHC.
After completion of study treatment, patients are followed every 3 months for 2 years.
- Conditions
- Breast Cancer
- Being tested
- bendamustine, erlotinib, Maintenance erlotinib
- Keywords
- male breast cancer, recurrent breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, estrogen receptor-negative breast cancer, HER2-negative breast cancer, progesterone receptor-negative breast cancer, triple-negative breast cancer
- Medical subject headings
- Breast Neoplasms, Breast Neoplasms, Male, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bendamustineDrug
Also called Ribomustin, Treanda, SDX- 105
100 or 120 mg/m2 IV on days 1 and 2
erlotinibDrug
Also called Tarceva
100 or 150 mg po on days 5 - 21 of each 28 day cycle
Maintenance erlotinibDrug
Also called Tarceva
150 mg po daily (days 1 - 28 of 28 day cycle)
| Study group | Role | What they receive |
|---|---|---|
| Bendamustine and Erlotinib | Experimental | Bendamustine 100 or 120 mg/m2 IV on days 1 and 2 and erlotinib 100 or 150 mg po on days 5 - 21 of each 28 day cycle. Receives: Drug: bendamustine; Drug: erlotinib; Drug: Maintenance erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I)
28 day cycle included intravenous bendamustine on days 1 and 2.
Measured: Up to two years
Maximum-tolerated Dose of Erlotinib Hydrochloride (Phase I)
28 day cycle included intravenous erlotinib on days 15-21.
Measured: Up to two years
Dose-limiting Toxicity (Phase I)
Measured: Up to two years
Progression-free Survival at 6 Months and 12 Months (Phase II)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: Up to two years
Secondary outcomes (5)
Objective Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to two years
Clinical Benefit Rate (CBR)
Measured: Up to two years
Duration of Response (DR)
Measured: Up to two years
Overall Survival (OS)
Measured: from time of study enrollment until death, for up to 2 years
Relationship of EGFR Expression or Amplification, Basal-like Tumors, and DNA Damage-repair Checkpoint Activation With ORR, CBR, DR, and OS
Measured: up to two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2009 (estimated)
- Study startApr 2009
- Primary completionAug 2013
- Study completionSep 2014
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 Ohio State University Comprehensive Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network, Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Rachel Layman, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00834678
- Sponsor's protocol ID
- OSU-08164
- Other IDs
- NCI-2011-03164
- Status last verified
- Mar 2018
- First submitted
- 31 Jan 2009
- Last updated
- 17 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Layman RM, Ruppert AS, Lynn M, Mrozek E, Ramaswamy B, Lustberg MB, Wesolowski R, Ottman S, Carothers S, Bingman A, Reinbolt R, Kraut EH, Shapiro CL. Severe and prolonged lymphopenia observed in patients treated with bendamustine and erlotinib for metastatic triple negative breast cancer. Cancer Chemother Pharmacol. 2013 May;71(5):1183-90. doi: 10.1007/s00280-013-2112-2. Epub 2013 Feb 21.
PubMed 23430121
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT00834678
- Acronym / sponsor ID
- OSU-08164
- Conditions
- Breast Cancer
- Keywords
- male breast cancer, recurrent breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, estrogen receptor-negative breast cancer, HER2-negative breast cancer, progesterone receptor-negative breast cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network, Genentech, Inc.
- Study start
- Apr 2009 (actual)
- Primary completion
- Aug 2013 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 3 Feb 2009 (estimated)
- Results
- Posted 22 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as bendamustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving bendamustine together with erlotinib may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving bendamustine together with erlotinib in treating patients with stage IIIB, stage IIIC, or stage IV breast cancer.
Detailed description
OBJECTIVES:
Primary
- To determine the phase II dose and assess the toxicity of bendamustine hydrochloride and erlotinib hydrochloride in patients with triple-receptor (estrogen receptor, progesterone receptor, and HER-2)-negative, stage IIIB, IIIC, or IV breast cancer. (Phase I)
- To determine the efficacy of this regimen in these patients. (Phase II)
Secondary (Correlative)
- To assess the correlation between tumor EGFR expression and EGFR gene amplification and treatment efficacy and toxicity.
- To assess for differences in treatment efficacy between basal-like and non-basal-like cancers.
- To assess for differences in treatment efficacy between tumors with and without expression of DNA damage-response (DDR) checkpoint proteins.
- To assess for differences in the activation state of DDR checkpoint proteins based on breast cancer subtype.
OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study.
Patients receive bendamustine hydrochloride IV over 30 minutes on days 1-2 and oral erlotinib hydrochloride once daily on days 5-21. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Patients with no evidence of disease progression may continue with daily single-agent oral erlotinib hydrochloride on days 1-28. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.
Breast cancer tissue blocks from prior procedures are obtained for correlative studies. After a tissue microarray (TMA) and a TMA map are prepared, TMA slides are used for hematoxylin and eosin (H\&E) staining, FISH, and IHC.
After completion of study treatment, patients are followed every 3 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bendamustine and Erlotinib | Experimental | Drug: bendamustine, Drug: erlotinib, Drug: Maintenance erlotinibBendamustine 100 or 120 mg/m2 IV on days 1 and 2 and erlotinib 100 or 150 mg po on days 5 - 21 of each 28 day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| bendamustineAlso: Ribomustin, Treanda, SDX- 105100 or 120 mg/m2 IV on days 1 and 2 | Drug | Bendamustine and Erlotinib |
| erlotinibAlso: Tarceva100 or 150 mg po on days 5 - 21 of each 28 day cycle | Drug | Bendamustine and Erlotinib |
| Maintenance erlotinibAlso: Tarceva150 mg po daily (days 1 - 28 of 28 day cycle) | Drug | Bendamustine and Erlotinib |
Primary outcome
Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I)
Time frame: Up to two years
28 day cycle included intravenous bendamustine on days 1 and 2.
Maximum-tolerated Dose of Erlotinib Hydrochloride (Phase I)
Time frame: Up to two years
28 day cycle included intravenous erlotinib on days 15-21.
Dose-limiting Toxicity (Phase I)
Time frame: Up to two years
Progression-free Survival at 6 Months and 12 Months (Phase II)
Time frame: Up to two years
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
5 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to two years
Clinical Benefit Rate (CBR)
Time frame: Up to two years
Duration of Response (DR)
Time frame: Up to two years
Overall Survival (OS)
Time frame: from time of study enrollment until death, for up to 2 years
Relationship of EGFR Expression or Amplification, Basal-like Tumors, and DNA Damage-repair Checkpoint Activation With ORR, CBR, DR, and OS
Time frame: up to two years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23430121Layman RM, Ruppert AS, Lynn M, Mrozek E, Ramaswamy B, Lustberg MB, Wesolowski R, Ottman S, Carothers S, Bingman A, Reinbolt R, Kraut EH, Shapiro CL. Severe and prolonged lymphopenia observed in patients treated with bendamustine and erlotinib for metastatic triple negative breast cancer. Cancer Chemother Pharmacol. 2013 May;71(5):1183-90. doi: 10.1007/s00280-013-2112-2. Epub 2013 Feb 21.
- JameslineLink provided by the sponsor.
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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.
Rachel Layman, MD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing bendamustine, erlotinib and Maintenance erlotinib in people with Breast Cancer, run by Ohio State University Comprehensive Cancer 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?
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 17 Apr 2018. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 22 Apr 2015). 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?
Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I) (time frame: Up to two years). The study lists 4 primary outcomes in all. 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 NCT00834678, 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 17 Apr 2018.