- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00734305
Phase I Safety Study of the Drug MM-121 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment
A Phase I and Pharmocologic Study of MM-121 in Patients With Refractory Advanced Solid Tumors
Studieöversikt
Detaljerad beskrivning
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 1
Kontakter och platser
Studieorter
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Massachusetts
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Boston, Massachusetts, Förenta staterna, 02115-6084
- Dana-Farber Cancer Institute
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Pennsylvania
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Philadelphia, Pennsylvania, Förenta staterna, 19111
- Fox Chase Cancer Center
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Tennessee
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Nashville,, Tennessee, Förenta staterna, 37232
- The Vanderbilt-Ingram Cancer Center
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Dose Escalation
Cohorts of escalating doses of MM-121 administered IV QW to determine MTD or RP2D + expansion cohort at MTD/RP2D
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Dose escalation Frequency - once weekly
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Objective Response Rate and Duration
Tidsram: Time from first dose to date of progression, with a median of 7.1 weeks
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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
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Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
Tidsram: From date of first dose to 30 days after termination, the longest 47 weeks
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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.
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From date of first dose to 30 days after termination, the longest 47 weeks
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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To Describe the Dose-limiting Toxicity of MM-121 as a Monotherapy
Tidsram: From date of first dose to 30 days after termination, the longest 47 weeks
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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.
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From date of first dose to 30 days after termination, the longest 47 weeks
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To Determine the Pharmacokinetic and Immunogenicity Parameters of MM-121
Tidsram: 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
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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
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To Determine the Pharmacokinetic Parameters of MM-121
Tidsram: 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).
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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
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Samarbetspartners och utredare
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Kwok Kin Wong, MD, Dana-Farber Cancer Institute
- Huvudutredare: Keedy L Vicki, MD, Vanderbilt University Medical Center
Publikationer och användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- MM-121-01-100
- MM-121
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
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