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Solid TumorPhase 1NCT02490475

A Multiple-Dose Study of RhuMab 2C4 and Docetaxel in the Treatment of Advanced Solid Tumors

A Phase 1 study testing Docetaxel and RhuMab 2C4 in people with Solid Tumor, run by Hoffmann-La Roche at 2 sites in 2 countries.

Completed

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

Official record
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Trial summary

This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of rhuMab 2C4 (Perjeta) and docetaxel (Taxotere) in participants with advanced solid tumors that have progressed during or after standard therapy, or for which no standard therapy is available. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
Docetaxel and RhuMab 2C4
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
2 sitesin 2 countries
Study dates
Feb 2004to Apr 2006
Phase
Phase 1
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

Who may be able to join

  • Adults at least 18 years of age
  • Easter Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy at least 12 weeks
  • Locally advanced or metastatic solid tumor with at least 1 measurable lesion, which has progressed during/after standard therapy
  • Human epidermal growth factor receptor 2 (HER2)-negative among participants with breast cancer
  • Negative pregnancy test or use of an adequate contraceptive method among women of childbearing potential
  • Adequate hematologic, hepatic, and renal function
  • Signed informed consent, histologically or cytologicall confirmed advanced solid tumor, adequate cardiac function as documented by LVEF >50% by ECHO or MUGA

Who cannot join

  • Clinical evidence of central nervous system (CNS) metastases
  • Prior chemotherapy, radiotherapy, or immunotherapy within 4 weeks, or hormone therapy within 2 weeks of study Day 1
  • History of neuropathy Grade 2 or worse, or any unresolved residual chemotherapy effects
  • Prior HER2-active agents or docetaxel
  • Any investigational agent within 28 days of study drug
  • Prior cumulative doxorubicin dose greater than (>) 360 mg/m^2 or equivalent
Show all 9Show fewer
  • Significant cardiovascular disease
  • Active/uncontrolled concurrent illness or infection-
  • Major surgery or trauma within 4 weeks of study Day 1

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Netherlands1 site
  • Study site

    Rotterdam, 3075 EA

Other trials in Netherlands

United Kingdom1 site
  • Study site

    Sutton, SM2 5PT

Other trials in United Kingdom

About this study

Official title: A Phase Ib, Open-Label, Multicenter Study of the Safety and Pharmacokinetics of the Combination of RhuMab 2C4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Docetaxel (Taxotere) in Patients With Advanced Solid Tumors

This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of rhuMab 2C4 (Perjeta) and docetaxel (Taxotere) in participants with advanced solid tumors that have progressed during or after standard therapy, or for which no standard therapy is available. Participants will be enrolled and evaluated for dose-limiting toxicities (DLTs) in escalating-dose cohorts in order to determine the maximum tolerated dose (MTD).

Conditions
Solid Tumor
Being tested
Docetaxel, RhuMab 2C4

What participants receive

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

  • DocetaxelDrug

    Also called Taxotere

    Participants will receive docetaxel on Day 1 of each 3-week cycle as 60, 75, or 100 mg/m^2 via IV infusion. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.

  • RhuMab 2C4Drug

    Also called Omnitarg

    Participants will receive rhuMab 2C4 on Day 1 of each 3-week cycle as 420 mg via IV infusion. For Cycle 1 ony, rhuMab will be administered on Day 2, at least 24 hours after docetaxel and following an initial 840-mg loading dose. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.

Study groups in NCT02490475
Study groupRoleWhat they receive
RhuMab 2C4 + Docetaxel 100 mg/m^2 (Level 3)ExperimentalDocetaxel will be administered via intravenous (IV) infusion on Day 1 of each 3-week cycle at a dose of 100 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
Receives: Drug: Docetaxel; Drug: RhuMab 2C4
RhuMab 2C4 + Docetaxel 60 mg/m^2 (Level 1)ExperimentalDocetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 60 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
Receives: Drug: Docetaxel; Drug: RhuMab 2C4
RhuMab 2C4 + Docetaxel 75 mg/m^2 (Level 2)ExperimentalDocetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 75 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
Receives: Drug: Docetaxel; Drug: RhuMab 2C4

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab

    A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.

    Measured: Cycle 1 Up to Day 15

Secondary outcomes (16)
  1. Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel

    The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity.

    Measured: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

  2. Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel

    Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as micrograms per milliliter (μg/mL).

    Measured: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

  3. Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel

    The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (μg*day/mL).

    Measured: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

  4. AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel

    The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as μg*day/mL.

    Measured: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

  5. Clearance (Cl) of Pertuzimab in Combination With Docetaxel

    Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day).

    Measured: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

  6. Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel

    The volume of distribution at steady state (Vz), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma.

    Measured: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

  7. Mean Residence Time (MRT) of Pertuzumab

    MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days.

    Measured: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22

  8. Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

    Best Overall response was evaluated as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). CR: complete disappearance of all target lesions. PR: at least a 30 percent (%) decrease in the sum of the longest diameters. SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameters since the treatment started. PD: at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit.

    Measured: Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks

  9. Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint

    Ejection fraction (EF) is the fraction of outbound blood pumped from the heart with each heartbeat. It is commonly measured by echocardiogram and serves as a general measure of a person's cardiac function. Changes in LVEF were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. The decrease in LVEF has been categorized as follows: A) Increase, no change, decrease from baseline less than (<) 10%; B) Absolute value <50% and decrease from baseline greater than or equal to (≥) 10%; C) Absolute value <50% and decrease from baseline≥15% ; D) Other. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit.

    Measured: Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22

  10. t1/2 for Docetaxel Alone and in Combination With Pertuzumab

    The biological half-life or terminal half-life of docetaxel is the time in hours it takes for it to lose half of its pharmacologic activity. Data for "docetaxel alone" arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

    Measured: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

  11. Tmax for Docetaxel Alone and in Combination With Pertuzumab

    Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; Data for "docetaxel alone" arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. When the rate of absorption equals the rate of elimination. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

    Measured: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

  12. Cmax for Docetaxel Alone and in Combination With Pertuzumab

    Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

    Measured: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

  13. AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab

    The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as ng*h/mL. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

    Measured: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

  14. Vss for Docetaxel Alone and in Combination With Pertuzumab

    The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

    Measured: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

  15. CL for Docetaxel Alone and in Combination With Pertuzumab

    Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per hour per meter squared (mL/h/m^2). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.

    Measured: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose

  16. Number of Participants With DLTs

    DLTs were defined as any of the following: 1) Any non-hematological toxicity greter than or equal to (≥) Grade 3 according t0 CTCAE version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.

    Measured: From Baseline until 4 weeks after the end of treatment

Timeline

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

  1. First posted3 Jul 2015 (estimated)
  2. Study startFeb 2004
  3. Primary completionApr 2006
  4. Study completionApr 2006

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02490475
Sponsor's protocol ID
BO17021
Status last verified
Apr 2017
First submitted
2 Jul 2015
Last updated
17 May 2017

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Docetaxel and RhuMab 2C4 in people with Solid Tumor, run by Hoffmann-La Roche at 2 sites in 2 countries.

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 8 inclusion and 9 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 17 May 2017. 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 Netherlands, United Kingdom. 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?

Yes. Results are posted in the registry (first posted 25 Nov 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 (MTD) of Docetaxel in Combination of Pertuzumab (time frame: Cycle 1 Up to Day 15). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 May 2017.

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