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Metastatic Breast CancerPhase 1/2NCT01306942

Dasatinib In Combination With Trastuzumab And Paclitaxel In First Line Treatment Of Her2-Positive MBC Patients

A Phase 1/2 study testing Dasatinib, Trastuzumab and Paclitaxel in people with Metastatic Breast Cancer, run by Spanish Breast Cancer Research Group at 8 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a single-arm, open-label, phase I/II study. In the phase I, patients with Human Epidermal Growth Factor Receptor 2 (HER2) positive MBC will be treated with paclitaxel, trastuzumab and increasing doses of dasatinib to determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Dasatinib, Trastuzumab and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
8 sitesSpain
Study dates
Jul 2011to 15 Mar 2019
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female with histologically confirmed breast cancer with documented metastasis.
  • Patients must have Human Epidermal Growth Factor Receptor 2 (HER2) overexpression by immunohistochemistry (3+, HercepTest®; DAKO) or a positive fluorescence in situ hybridization for HER2 amplification evaluated by central laboratory. It is recommended that a formalin-fixed paraffin embedded (FFPE) tumor tissue block from the metastatic site (or the primary tumor, if metastatic site not available) required for HER2 testing are provided.
  • Patients can have measurable or non measurable disease for the Phase I part. For the Phase II only patients with measurable disease defined per RECIST 1.1 will be included.
  • Signed Written Informed Consent.
  • Target Population:
  • Patients with Performance Status (ECOG) of 0 or 1.
Show all 18Show fewer
  • Number of previous therapies allowed or previous therapies may have included:
  • Chemotherapy: no prior chemotherapy for MBC is permitted. Patients treated with adjuvant chemotherapy regimens based on taxanes are allowed to be included if they are fully recovered of any taxane associated toxicity and a minimum of 12 months have elapsed from the end of this therapy.
  • Hormonal Therapy: patients may have had prior hormonal therapy. All hormonal agents must be discontinued at least 3 weeks prior to study entry.
  • Radiation Therapy: patients may have had prior radiation therapy that has not exceeded 25% of the bone marrow reserve. A minimum of 21 days must have elapsed between the last dose of radiation and registration into the study. Patients must have recovered from any acute toxic effects from radiation prior to registration. Lesions that have been irradiated cannot be included as sites of measurable disease for the phase II unless clear tumor progression, according to RECIST criteria, has been documented in these lesions since the end of radiation therapy.
  • Previous Surgery: previous surgery is permitted provided that wound healing has occurred.
  • Anti-HER2 Therapies: no prior anti-HER2 therapy for MBC is permitted. Patients treated with adjuvant anti-HER2 therapies (including but not limited to trastuzumab and lapatinib) are allowed to be included if a minimum of 12 months have elapsed from the end of this therapy.
  • Adequate Organ Function (...).
  • Ability to take oral medication (dasatinib must be swallowed whole).
  • Concomitant Medications
  • Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib) ii) Biphosphonates must not be initiated within 28 days prior to study therapy
  • Age and sex:
  • Patient, age 18 years old. g) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 4 weeks after the last dose of study drug to minimize the risk of pregnancy. (...)

Who cannot join

  • Sex and reproductive status:
  • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug
  • Women who are pregnant or breastfeeding.
  • Women with a positive pregnancy test
  • Target Disease Exceptions:
  • Central nervous system (CNS) metastases which are not well controlled. Eligible patients must be asymptomatic, cannot be receiving steroids or anticancer treatment, and must be enrolled at least 1 month after the end of the radiotherapy treatment
Show all 26Show fewer
  • Medical History and Concurrent Diseases
  • No malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 5 years.
  • Concurrent medical condition which may increase the risk of toxicity, including: Pleural or pericardial effusion of any grade.
  • Cardiac Symptoms; any of the following should be considered for exclusion:
  • Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months) ii). Patients with intercurrent cardiac dysfunction or left ventricular ejection fraction (LVEF) < 50%.
  • Diagnosed congenital long QT syndrome. iv) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
  • Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (450 msec).
  • Patients with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
  • History of significant bleeding disorder unrelated to cancer, including: i) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease). ii) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
  • Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.
  • Allergies and Adverse Drug Reactions
  • Patients with known allergy to any of the study drugs or their components.
  • Prohibited Treatments and/or Therapies
  • Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib) i) quinidine, procainamide, disopyramide ii) amiodarone, sotalol, ibutilide, dofetilide iii) erythromycin, clarithromycin iv) chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide v) cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
  • Concurrent anti-cancer therapy c) Potent CYP3A4 inhibitors
  • Other exclusion criteria:
  • Patients who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
  • Patients with active or uncontrolled infections or with serious illnesses or medical conditions that would not permit the patient to be managed according to the protocol.
  • Patients unable or unwilling to give written informed consent prior to study participation.
  • Pre-existent motor or sensory neurotoxicity of severity ≥ grade 2 according to NCI common toxicity criteria (version 4.03).

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Spain8 sites

  • Complejo Hospitalario Universitario A Coruña

    A Coruña, 15006

  • Hospital Clinic i Provincial

    Barcelona, 08036

  • Instituto Catalán de Oncología de Barcelona (Hospital Duran i Reynalds)

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007

  • Hospital Clínico Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Instituto Valenciano de Oncología

    Valencia, 46009

  • Hospital Alvaro Cunqueiro

    Vigo, Pontevedra, 36204

Other trials in Spain

About this study

Official title: A Phase I/II Trial of Dasatinib in Combination With Trastuzumab and Paclitaxel in the First Line Treatment of Her2-Positive Metastatic Breast Cancer (MBC) Patients

This is a single-arm, open-label, phase I/II study. In the phase I, patients with Human Epidermal Growth Factor Receptor 2 (HER2) positive MBC will be treated with paclitaxel, trastuzumab and increasing doses of dasatinib to determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RPD) of the combination. Once the RPD has been identified, 48 patients will be treated at that dose to evaluate the efficacy and safety of the combination in the phase II.

Read the detailed description

Eligible patients will be enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib will be administered orally in two dose levels 100 and 140 mg once daily (a -1 dose level is included just in case dose de-escalation is needed). Treatment will be repeated on Day 1 of a 28-day cycle in all patients (both in the phase I as in the phase II) until radiographic or symptomatic progression or unacceptable toxicity occurs. Only in the phase I and in all patients included in every different dose level, the first cycle will last 38 days.

Primary Objective:

  • To determine the maximum tolerated dose (MTD) and recommended phase II dose (RPD) of dasatinib in combination with fixed doses of trastuzumab and paclitaxel in HER2-positive MBC patients (Phase I).
  • To determine the efficacy, measured by objective response rate (ORR) in HER2-positive MBC patients with measurable disease (Phase II).

Secondary Objective(s):

  • To characterize the safety of the combination (in both phase I and phase II).
  • To evaluate the Clinical Benefit Rate (CBR), Time to Progression (TTP), Progression Free Survival (PFS) and Response Duration (RD) (in the phase II).
  • To evaluate the pharmacokinetics (PK) of the combination (in the phase I and selected patients in the phase II if necessary).
  • To evaluate molecular characteristics that may be predictive of the activity (or lack of) and any correlation between the biological activity of the study treatment and the disease outcome.

Exploratory objective:

  • To explore the correlation between the lymphocytosis and efficacy.

Sample Size:

Phase I: following the 3+3 rule, a minimum of 6 and a maximum of 12 patients will be recruited.

Phase II:Assuming 10% drop-out rate, 48 patients are required to enter the study.

The duration of the study, from first patient visit to last patient visit will be approximately 42 months.

Keywords
HER2 positive breast cancer, first line treatment, Dasatinib, SRC kinase, Trastuzumab resistance
Medical subject headings
Breast Neoplasms

What participants receive

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

Study groups in NCT01306942
Study groupRoleWhat they receive
Dasatinib + trastuzumab + paclitaxelExperimentalEligible patients will be enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib will be administered orally in two dose levels 100 and 140 mg once daily (QD) (a -1 dose level is included just in case dose de-escalation is needed). Treatment will be repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occurs. Only in the phase I, the first cycle will last 38 days.
Receives: Drug: Dasatinib; Drug: Trastuzumab; Drug: Paclitaxel

What is being measured

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

  1. Number of Participants With Dose Limiting Toxicity (DLT) Within the First Cycle of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I)

    DLT was defined as the occurrence of any of the following adverse events or abnormal laboratory value (graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03), assessed as possibly, probably or definitively related to study drugs, occurring within the first cycle of study treatment: Need of any dose modification within the first cycle due to toxicity, grade 3 or 4 neutropenia complicated with fever ≥38.5° C or infection, grade 4 neutropenia (absolute neutrophil count (ANC)<0.5x1000000000/L) of at least 7 days duration, grade 3 thrombocytopenia complicated by hemorrhage, grade 4 thrombocytopenia, any grade 4 non-hematologic toxicity, grade 3 non-hematologic toxicities except nausea, vomiting, or diarrhea that can be controlled by appropriate medical intervention or prophylaxis, inability to resume dosing for cycle 2 at the current dose level within 14 days due to treatment related toxicity.

    Measured: Up to cycle 1

  2. Maximum Tolerated Dose (MTD) of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I)

    MTD is determined by testing increasing doses of dasatinib on dose escalation cohorts 3 to 6 patients per dose level. MTD reflects the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels

    Measured: Up to cycle 1

  3. Recommended Phase II Dose (RP2D) of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I).

    The RP2D was decided by the investigators taken into consideration the information obtained in the study and based on the MTD. To define the RP2D, information about toxicity observed during the full treatment were taken into consideration (relative dose intensity and toxicity observed).

    Measured: Up to cycle 1

  4. Objective Response Rate (ORR)

    Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. ORR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) out of the patients who had measurable disease at baseline. Per RECIST, Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as an >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Through study treatment, an average of 24 months

Secondary outcomes (16)

  1. The Number of Participants Who Experienced Adverse Events (AE)

    Safety was assessed by standard clinical (blood pressure, pulse and body temperature, electrocardiogram (ECG), left ventricular ejection fraction (LVEF)) and laboratory tests (hematology: hemoglobin, platelet count, red blood cells (RBC), white blood cells (WBC) with differential (neutrophils) and absolute lymphocyte count, and serum chemistry: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, sodium, potassium, magnesium, phosphate and calcium). Adverse events grade were defined by the NCI CTCAE v 4.03.

    Measured: Through study treatment, an average of 24 months

  2. To Evaluate the Clinical Benefit Rate (CBR)

    Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CBR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) plus stable disease lasting at least 6 months out of the efficacy population. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Through study treatment, an average of 24 months

  3. Time to Progression (TTP)

    TTP is defined as the time from the date of the first dose to the first date of objectively determined progressive disease. For patients not known to have objectively-determined progressive disease, TTP will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression, TTP will be censored at the date of last objective progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy.

    Measured: Through study treatment, an average of 24 months

  4. Progression Free Survival (PFS)

    PFS is defined as the time from the date of the first dose to the first date of objectively determined progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objectively-determined progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy.

    Measured: Through study treatment, an average of 24 months

  5. Response Duration (RD)

    Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. RD is defined as the time from the date when the measurement criteria are met for complete response (CR) or partial response (PR) (whichever status is recorded first) until the date of first observation of disease progression or death occurred. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions. For responding patients not known to have died as of the data cut-off date and who do not have progression, RD will be censored at the date of last visit with adequate assessment. For responding patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to progression, RD will be censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy.

    Measured: Through study treatment, an average of 24 months

  6. Dasatinib Maximun Plasma Concentration (Cmax) Value (Pharmacokinetics (PK) Phase I)

    To assess the influence of the concomitant administration of paclitaxel and trastuzumab on dasatinib PKs, we compared dasatinib exposures alone (first PK occasion: day 2 of cycle 1) or combined (second PK occasion: day 18 on cycle 1).

    The mean profiles of dasatinib plasma concentrations were determined by dose and PK occasion.

    Measured: Cycle 1 day 2 and day 18

  7. Dasatinib Area Under the Plasma Concentration-time Curve (AUC) Value (Pharmacokinetics (PK) Phase I)

    To assess the influence of the concomitant administration of paclitaxel and trastuzumab on dasatinib PKs, we compared dasatinib exposures alone (first PK occasion: day 2 of cycle 1) or combined (second PK occasion: day 18 on cycle 1).

    The area under the plasma concentration-time curve from time zero to 8 hours post dose (AUC0-8) were calculated in all treated patients, as the dasatinib plasmatic half-life is very short and concentrations at 24 hours post dose could only be quantified in some patients.

    Measured: Cycle 1 day 2 and day 18

  8. Phosphorylated SRC (p-SRC) Protein Expression Change in Peripheral Blood Mononuclear Cells After 8 Hours of Treatment (Phase II)

    Sequential peripheral blood mononuclear cells (PBMCs) on Cycle 1 Day 1 before treatment and 8 hours (h) after treatment (0h and 8h) were assessed to explore changes in the expression of p-SRC proteins measured by enzyme-linked immunosorbent assay (ELISA). For ELISA analyses, a duplicate of 100 µg of the extract was used to detect p-SRC (Tyr416). ELISA is a plate-based assay technique designed for detecting and quantifying proteins. The instrumentation used for protein signal-detection is an absorbance spectrophotometer (AS), which measures Absorbance (A). A is the quantity of light absorbed by a sample. As different compounds absorb light at different wavelengths, an AS can be used to distinguish compounds by analyzing the pattern of wavelengths absorbed by a given sample. Additionally, the amount of light absorbed is directly proportional to the concentration of absorbing compounds in that sample, so an AS can also be used to determine concentrations of compounds in the sample.

    Measured: Cycle 1 day 1 at 0 hours and at 8 hours

  9. Phosphorylated AKT (p-AKT) Protein Expression Change in Peripheral Blood Mononuclear Cells After 8 Hours of Treatment (Phase II)

    Sequential peripheral blood mononuclear cells (PBMCs) on Cycle 1 Day 1 before treatment and 8 hours (h) after treatment (0h and 8h) were assessed to explore changes in the expression of p-AKT proteins measured by enzyme-linked immunosorbent assay (ELISA). For ELISA analyses, a duplicate of 100 µg of the extract was used to detect p-AKT (Ser473). ELISA is a plate-based assay technique designed for detecting and quantifying proteins. The instrumentation used for protein signal-detection is an absorbance spectrophotometer (AS), which measures Absorbance (A). A is the quantity of light absorbed by a sample. As different compounds absorb light at different wavelengths, an AS can be used to distinguish compounds by analyzing the pattern of wavelengths absorbed by a given sample. Additionally, the amount of light absorbed is directly proportional to the concentration of absorbing compounds in that sample, so an AS can also be used to determine concentrations of compounds in the sample.

    Measured: Cycle 1 day 1 at 0 hours and at 8 hours

  10. Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase I)

    p-SRC was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 and cycle 2 day 1, only in patients accepting to participate.

    A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

    Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of SRC.

    Measured: Cycle 1 day 1 at 0 hours and at 8 hours, cycle 1 day 4 and cycle 2 day 1

  11. Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase II)

    p-SRC was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, only in patients accepting to participate.

    A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

    Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of SRC.

    Measured: Cycle 1 day 1 at 0 hours and at 8 hours

  12. Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase I)

    p-AKT was analyzed in the skin biopsies taken at cycle 1, day 1 at 0 hours and 8 hours, and cycle 2 day 1, only in patients accepting to participate.

    A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

    Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of AKT

    Measured: Cycle 1 day 1 at 0 hours and at 8 hours and cycle 2 day 1

  13. Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase II)

    p-AKT was analyzed in the skin biopsies taken at cycle 1, day 1 at 0 hours and 8 hours, only in patients accepting to participate.

    A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

    Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of AKT

    Measured: Cycle 1 day 1 at 0 hours and at 8 hours

  14. Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase I)

    p-ERK was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 at 8 hours, and cycle 2 day 1 at 8 hours, only in patients accepting to participate.

    A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

    Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of ERK

    Measured: Cycle 1 day 1 at 0 hours and at 8 hours, cycle 1 day 4 at 8 hours and cycle 2 day 1 at 8 hours

  15. Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase II)

    Phosphorylated extracellular signal-regulated kinases (p-ERK) 1 and 2 expression were analyzed in the skin biopsies taken at the cycle 1 day 1 at 0 hours and 8 hours, only in patients accepting to participate.

    A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

    Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of ERK

    Measured: Cycle 1 day 1 at 0 hours and at 8 hours

  16. Number of Participants With Correlation Between Lymphocytosis and Efficacy.

    Efficacy (ORR, CBR, TTP, RD and PFS) was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria, and were correlated Lymphocytes, that were measured in the weekly hematology analyses performed within the first cycle.

    Measured: Cycle 1

Timeline

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

  1. First posted2 Mar 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionDec 2013
  4. Study completion15 Mar 2019

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01306942
Sponsor's protocol ID
GEICAM/2010-04
Other IDs
2010-023304-27
Status last verified
Mar 2023
First submitted
24 Feb 2011
Last updated
30 Mar 2023
Data monitoring committee
No

Publications

  • Ocana A, Gil-Martin M, Antolin S, Atienza M, Montano A, Ribelles N, Urruticoechea A, Falcon A, Pernas S, Orlando J, Montero JC, Escudero MJ, Benito S, Caballero R, Carrasco E, Rojo F, Pandiella A, Ruiz-Borrego M. Efficacy and safety of dasatinib with trastuzumab and paclitaxel in first line HER2-positive metastatic breast cancer: results from the phase II GEICAM/2010-04 study. Breast Cancer Res Treat. 2019 Apr;174(3):693-701. doi: 10.1007/s10549-018-05100-z. Epub 2019 Jan 3.

    PubMed 30607629

  • Ocana A, Gil-Martin M, Martin M, Rojo F, Antolin S, Guerrero A, Trigo JM, Munoz M, Pandiella A, Diego NG, Bezares S, Caballero R, Carrasco E, Urruticoechea A. A phase I study of the SRC kinase inhibitor dasatinib with trastuzumab and paclitaxel as first line therapy for patients with HER2-overexpressing advanced breast cancer. GEICAM/2010-04 study. Oncotarget. 2017 Apr 14;8(42):73144-73153. doi: 10.18632/oncotarget.17113. eCollection 2017 Sep 22.

    PubMed 29069857

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dasatinib, Trastuzumab and Paclitaxel in people with Metastatic Breast Cancer, run by Spanish Breast Cancer Research Group at 8 sites in Spain.

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 18 inclusion and 26 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 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Spain. 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 9 Sep 2019). 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?

Number of Participants With Dose Limiting Toxicity (DLT) Within the First Cycle of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I) (time frame: Up to cycle 1). 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 NCT01306942, which also lists 2 linked publications.

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 Mar 2023.

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