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Triple Negative Metastatic Breast CancerPhase 1NCT02358200

Study of BMN-673 With Carboplatin and Paclitaxel in Patients With Advanced BRCA-mutated Solid Tumor or Triple Negative Metastatic Breast Cancer

A Phase 1 study testing BMN-673, Carboplatin and Paclitaxel in people with Triple Negative Metastatic Breast Cancer and BRCA-mutated Solid Tumor, run by Pamela Munster at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Open label, non-randomized, dose escalation and expansion Phase Ia/b trial to evaluate the safety of the combination of BMN 673 and carboplatin, and subsequently BMN 673 in combination with paclitaxel and carboplatin to determine the recommended Phase II dose of the combination. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BMN-673, Carboplatin and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
23 Feb 2015to 8 Jan 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

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

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

Who may be able to join

  • Men and women, 18 years or older with advanced malignancies for which no standard therapy is available.
  • Dose Escalation: Patients with any solid tumor malignancies
  • Does Expansion:
  • Patients with advanced malignancies that have germline and/or somatic BRCA mutations (cohort gBRCA) Or
  • Triple negative (TN) metastatic breast cancer without known BRCA mutation (cohort TNBC). Tumors will be considered TN when:
  • Estrogen receptor (ER) expression <1%
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  • Progesterone receptor (PR) expression <1%
  • Her2 negative as per the American Society of Clinical Oncology (ASCO) guidelines
  • Paclitaxel expansion: any solid tumor malignancy with potential benefit from this combination and paclitaxel (ASP).
  • Dose expansion cohort only: Histological or cytological confirmation of advanced unresectable solid tumors for which no standard therapy is available in patients with a known BRCA germline mutation or those with metastatic triple negative breast cancer without known BRCA mutation (see inclusion criteria one for definition of triple negative breast cancer).. For the paclitaxel cohorts, any solid tumors with potential benefit from this combination and paclitaxel.
  • Consent to screening tumor biopsy (for accessible tumors when appropriate) [optional in dose escalation, mandatory in dose expansion]
  • Part 2 only: Measureable tumor (RECIST1.1)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
  • Adequate organ function:
  • Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
  • Hemoglobin (Hgb) ≥9.5 g/dL(transfusion before treatment is allowable if more than 3 days prior to study start)
  • Platelets (plt) ≥ 100 x 109/L
  • Potassium within normal range, or correctable with supplements;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x Upper Limit Normal (ULN)
  • Serum total bilirubin ≤ 1.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance ≥ 60ml/min
  • Females of child-bearing potential (FCBP) must have negative serum pregnancy test within 7 days before starting study treatment and willingness to adhere to acceptable forms of birth control (a physician-approved contraceptive method: oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) for a minimum of 4 weeks following the discontinuation of study treatment.
  • FCBP is defined as a sexually mature woman who:
  • Has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or,
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time during the preceding 12 consecutive months
  • Male subjects with female partner of childbearing potential must agree to the use of a physician-approved contraceptive method throughout the course of the study and for a minimum of 4 weeks following the discontinuation of study treatment.
  • Ability to take oral medications

Who cannot join

  • Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks, whichever is shorter, prior to starting study treatment
  • Patients must have recovered from side effects from prior cancer-directed therapy to grade 1 or less (unless deemed not clinically significant by study investigator).
  • Major surgery ≤ 4 weeks prior to starting study regimen or who have not recovered from surgery.
  • Any known unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
  • History of myocardial infraction (MI) within 6 month prior to starting study treatment.
  • Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
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  • Any condition that confounds the ability to interpret data from the study.
  • Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 4 weeks are allowed.
  • Malabsorption or uncontrolled peptic ulcer disease
  • Grade 2 or higher peripheral neuropathy (paclitaxel arm only)
  • Known allergic reaction or poor tolerability to PARP inhibitors, carboplatin, or paclitaxel
  • Pregnant or breastfeeding
  • Known active human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California San Francisco

    San Francisco, California, 94115

Other trials in United States

About this study

Official title: Phase I Study to Evaluate the Tolerability, Safety and Efficacy of BMN-673 in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumor Malignancies That Have BRCA Mutations or Triple Negative Metastatic Breast Cancer

Open label, non-randomized, dose escalation and expansion Phase Ia/b trial to evaluate the safety of the combination of BMN 673 and carboplatin, and subsequently BMN 673 in combination with paclitaxel and carboplatin to determine the recommended Phase II dose of the combination.

Read the detailed description

Poly adenosine diphosphate-ribose polymerase (PARP) 1/2 inhibitors are a novel class of anticancer agents that have shown activity in tumors with defects in DNA repair and may induce synthetic lethality in combination with agents that induce DNA damage by preventing DNA repair.

The rationale of this study is to determine whether a DNA damaging agent can potentiate the cell death induced by PARP inhibitors in individuals with tumor that are more susceptible to chemotherapy.

The study will evaluate the potential benefits of BMN 673 in combination with weekly carboplatin in patients with metastatic tumors associated with BRCA germ line mutations or patients with triple negative breast cancer with no known BRCA mutation, subsequently if tolerated, an additional cohort will examine the feasibility of adding paclitaxel to this combination for any solid tumor malignancies with potential benefit to this combination.

This is the first study to evaluate the safety and efficacy of BMN 673 in combination with carboplatin in patients with either BRCA mutations or TNBC. If tolerable paclitaxel will be added to the combination in any solid tumor malignancies with potential benefit to this combination.

Being tested
BMN-673, Carboplatin, Paclitaxel

What participants receive

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

Study groups in NCT02358200
Study groupRoleWhat they receive
TreatmentExperimentalBMN-673: Oral, every day, Days 1-21; Carboplatin: intravenous, every week, 750 μg/day; Paclitaxel: intravenous, every week, 0.75 x Maximum Tolerated Dose μg/day
Receives: Drug: BMN-673; Drug: Carboplatin; Drug: Paclitaxel

What is being measured

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

  1. Overall Response Rate (ORR)

    Response rate of combination (BMN 673 + carboplatin) in patients with BRCA germline mutations or triple negative cancer without known BRCA mutations, in solid tumor malignancies with paclitaxel with a 15 patient cohort expansion at the maximum tolerated dose (MTD). Response and progression in this study will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

    Measured: From date of randomization until the date of Initial response to the first documented tumor progression or date of death from any cause, up to 18 months.

Secondary outcomes (1)

  1. Intolerable Toxicity

    Analyses of adverse events will be performed for all patients having received at least one dose of study drug. The study will use the CTCAE v4.0 for reporting of non-hematologic adverse events.

    Measured: From first dose to 30 day follow up.

Timeline

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

  1. First posted6 Feb 2015 (estimated)
  2. Study start23 Feb 2015
  3. Primary completion8 Jan 2019
  4. Study completion8 Jan 2019

Why it stopped: Funding support for the study was terminated

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02358200
Sponsor's protocol ID
14955
Status last verified
Jan 2020
First submitted
27 Jan 2015
Last updated
10 Jan 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BMN-673, Carboplatin and Paclitaxel in people with Triple Negative Metastatic Breast Cancer and BRCA-mutated Solid Tumor, run by Pamela Munster 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 27 inclusion and 13 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 10 Jan 2020. 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 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.

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

Are results available for this study?

The study was stopped early (reason given: Funding support for the study was terminated). Results are not available in the source record.

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?

Overall Response Rate (ORR) (time frame: From date of randomization until the date of Initial response to the first documented tumor progression or date of death from any cause, up to 18 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 NCT02358200.

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 10 Jan 2020.

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