Phase 1 Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C
|ClinicalTrials.gov Identifier: NCT01577758|
Recruitment Status : Completed
First Posted : April 16, 2012
Results First Posted : July 25, 2016
Last Update Posted : September 7, 2016
|Condition or disease||Intervention/treatment||Phase|
|Advanced Gastrointestinal Malignancies||Drug: MLN0264||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C|
|Study Start Date :||June 2012|
|Primary Completion Date :||February 2014|
|Study Completion Date :||February 2014|
MLN0264 starting dose 0.3 mg/kg escalated until Maximum Tolerated Dose (MTD) was determined, 30-minute infusion, on Day 1 of each 21-Day treatment cycle.
MLN0264 30-minute infusion on Day 1 of each treatment cycle
- Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months ]
DLT was defined as any of the following Adverse Events (AEs) that occur and are considered by the investigator to be related to therapy.
- Grade 4 neutropenia (Absolute Neutrophil Count < 500 cells/mm^3).
- Grade 3 or greater neutropenia with fever and/or infection.
- Grade 4 thrombocytopenia (platelets < 25,000/mm^3).
- Grade 3 or greater thrombocytopenia with clinically meaningful bleeding at any time.
- Grade 3 or greater nausea and/or emesis that occurs despite of prophylaxis.
- Grade 3 or greater diarrhea that occurs despite supportive care.
- Any other Grade 3 or greater non-hematological toxicity other than Grade 3 fatigue or Grade 3 Alopecia.
- Inability to start the next cycle of therapy due to treatment delay of more than 2 weeks because of lack of recovery.
- Other MLN0264-related non-hematologic toxicities Grade 2 or greater requiring discontinuation of therapy.
- Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months ]
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
- Maximum Tolerated Dose (MTD) of MLN0264 [ Time Frame: Every 3 weeks until MTD is established, approximately 9 months ]MTD of MLN0264 was determined. Decisions regarding dose escalation were made based on any DLT that occurred during the first cycle of treatment.
- Cmax: Maximum Observed Serum Concentration for MLN0264 [ Time Frame: Cycle 1: Day 1 pre-dose to Day 21 post-dose ]Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably.
- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) [ Time Frame: Cycle 1: Day 1 pre-dose to Day 21 post-dose ]Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably.
- AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MLN0246 [ Time Frame: Cycle 1: Day 1 pre-dose to 21 Days post-dose ]Area under the drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably.
- AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MMAE [ Time Frame: Cycle 1: Day 1 pre-dose to 21 Days post-dose ]Area under the plasma drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably.
- Best Overall Response [ Time Frame: At the completion of every second cycle up to 12 cycles (approximately 9 months). Each cycle is a 21 days cycle ]
The percentage of participants in each best overall response category, was determined using the Modified Response Evaluation Criteria in Solid Tumors (RECIST).
Complete Response: Disappearance of all target lesions and all non-target lesions and normalization of tumor marker level.
Partial Response: At least a 30% decrease in the sum of the Longest Diameter (LD) of target lesions, taking as reference the baseline sum LD.
Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the start or the appearance of one or more new lesions. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
- Number of Participants With Antitherapeutic Antibodies (ATA) [ Time Frame: Day 1 of every 21 days cycle and at End of study (EOS) approximately 9 months ]Blood was collected and sent to a laboratory to determine the immunogenicity, whether binding antibodies to MLN0264 were present (ATA development).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01577758
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|Study Director:||Medical Monitor||Millennium Pharmaceuticals, Inc.|