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Phase I Safety Study of the Drug MM-121 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment

30. august 2016 opdateret af: Merrimack Pharmaceuticals

A Phase I and Pharmocologic Study of MM-121 in Patients With Refractory Advanced Solid Tumors

This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design to determine maximum tolerated dose/recommended Phase 2 dose.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Successive cohorts of three or more patients were treated at escalating doses until a maximum tolerated dose/recommended phase 2 dose was identified. The study initially explored a dosing schedule every 7-days, which may have been modified to longer intervals under certain circumstances but did not expand to more than weekly. When the maximum tolerated dose/recommended Phase 2 dose was identified, an Expansion Cohort was enrolled at that dose to further characterize safety and to explore pharmacodynamic endpoints. There were 3 sites that participated.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

44

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02115-6084
        • Dana-Farber Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19111
        • Fox Chase Cancer Center
    • Tennessee
      • Nashville,, Tennessee, Forenede Stater, 37232
        • The Vanderbilt-Ingram Cancer Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed advanced solid tumors that have recurred or progressed following standard therapy, or that have not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
  • Patients must be > 18 years of age
  • Patients or their legal representatives must be able to understand and sign an informed consent form

  • Patients must have evaluable or measurable tumor(s)

    • Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for patients with known peripheral neuropathy.
    • Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-121 (an effective form of contraception is an oral contraceptive or a double barrier method)

In addition, patients to be enrolled the Expansion Cohort must have/be:

  • Advanced/metastatic breast cancer with histological/cytological documentation of ER-, PR-, Her2/neu non-over-expressing breast cancer (triple negative breast cancer); OR,
  • Patients must have advanced/metastatic breast cancer with histologically or cytologically confirmed ER+ and/or PR+, Her2/neu non-over-expxressing OR,
  • Patients must have advanced/metastatic histological confirmation of epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer; OR,
  • Additional tumor types such as metastatic colorectal, advanced non small cell lung cancer, and others may be considered on a per-patient basis
  • Tumor tissue amenable to biopsy
  • Platelet counts, partial thromboplastin time (PTT) and international normalized ratio (INR) within normal limits.
  • Willing to undergo tumor biopsy twice (once before and once after treatment with MM-121)
  • Blocks of archived formalin-fixed, paraffin-embedded, unstained tumor tissue available for submission. Patients with no available archived tumor tissue available must receive Sponsor approval prior to enrollment.

Exclusion Criteria:

  • Patients for whom potentially curative antineoplastic therapy is available
  • Patients who are pregnant or lactating
  • Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled.)
  • Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial
  • NYHA Class III or IV congestive heart failure or LVEF < 55%
  • Known HIV, hepatitis B or C (active, previously treated or both)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Dose Escalation
Cohorts of escalating doses of MM-121 administered IV QW to determine MTD or RP2D + expansion cohort at MTD/RP2D
Medicin: MM-121
Dose escalation Frequency - once weekly
Andre navne:
  • Seribantumab, SAR256212

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Objective Response Rate and Duration
Tidsramme: Time from first dose to date of progression, with a median of 7.1 weeks

To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response is defined as a >20% decrease in tumor burden from baseline and a Complete Response is defined as complete disappearance of tumor burden from baseline. Duration of response is defined as the length of time in weeks from observation of response until progression.

NOTE: because no patients experienced an objective response as shown below, duration of response is not presented. No duration of response could be measured.
Time from first dose to date of progression, with a median of 7.1 weeks
Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
Tidsramme: From date of first dose to 30 days after termination, the longest 47 weeks
Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort from cohort 1-6. Cohort 1 began at 3.2 mg/kg IV QW and the dose escalated in separate cohorts from 6 mg/kg IV QW, 10 mg/kg IV QW, 15 mg/kg IV QW, 20 mg/kg IV QW, to the highest scheduled testing dose at 40 mg/kg one-time loading dose on cycle 1, week 1 followed by 20 mg/kg IV QW maintenance doses. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose and was used to open the expansion cohort.
From date of first dose to 30 days after termination, the longest 47 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
To Describe the Dose-limiting Toxicity of MM-121 as a Monotherapy
Tidsramme: From date of first dose to 30 days after termination, the longest 47 weeks
To establish the safety of escalating doses of MM-121 administered as a monotherapy in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.
From date of first dose to 30 days after termination, the longest 47 weeks
To Determine the Pharmacokinetic and Immunogenicity Parameters of MM-121
Tidsramme: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg).

Immunogenicity data is not available.
At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
To Determine the Pharmacokinetic Parameters of MM-121
Tidsramme: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The AUC is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg).
At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Merrimack Pharmaceuticals

Samarbejdspartnere

Sanofi

Efterforskere

  • Ledende efterforsker: Kwok Kin Wong, MD, Dana-Farber Cancer Institute
  • Ledende efterforsker: Keedy L Vicki, MD, Vanderbilt University Medical Center

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. juli 2008

Primær færdiggørelse (Faktiske)

1. maj 2010

Studieafslutning (Faktiske)

1. september 2013

Datoer for studieregistrering

Først indsendt

12. august 2008

Først indsendt, der opfyldte QC-kriterier

12. august 2008

Først opslået (Skøn)

14. august 2008

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

1. september 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

30. august 2016

Sidst verificeret

1. august 2016

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • MM-121-01-100
  • MM-121

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

Ingen

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Kliniske forsøg med Avancerede solide tumorer

Kliniske forsøg med MM-121

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