Clinical trial NCT01577758: Phase 1 Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Gastrointestinal Malignancies
Keywords: Phase 1,
Advanced gastrointestinal malignancies,
MLN0264,
Guanylyl Cyclase C(GCC),
Antibody Drug Conjugate(ADC)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-04-16
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an Open-Label, Multicenter, Dose Escalation, First-in-Human Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C.


Eligibility criteria: Inclusion Criteria:

* Voluntary consent form
* Diagnosis of GI malignancy with a GCC protein expressing tumor
* Male or female patients 18 years or older with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
* Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
* Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate bone marrow, hepatic and renal function as specified in the protocol

Exclusion Criteria:

* Female patients who are lactating or have a positive serum pregnancy test during the screening period
* Any serious medical or psychiatric illness that could interfere with the completion of treatment
* Major surgery or treatment with investigational drug before the first dose
* Serious infection within 14 days before the first dose of study drug
* Known HIV, inflammatory bowel disease, viral hepatitis or cerebral/meningeal brain metastases
* Patients with cardiovascular conditions specified in protocols
* Patients with history of another primary malignancy not in remission for at least 3 years

Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons.

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months
measure: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
timeFrame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months
measure: Maximum Tolerated Dose (MTD) of MLN0264
timeFrame: Every 3 weeks until MTD is established, approximately 9 months
measure: Cmax: Maximum Observed Serum Concentration for MLN0264
timeFrame: Cycle 1: Day 1 pre-dose to Day 21 post-dose
measure: Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)
timeFrame: Cycle 1: Day 1 pre-dose to Day 21 post-dose
measure: AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MLN0246
timeFrame: Cycle 1: Day 1 pre-dose to 21 Days post-dose
measure: AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MMAE
timeFrame: Cycle 1: Day 1 pre-dose to 21 Days post-dose
Secondary outcomes:
measure: Best Overall Response
timeFrame: At the completion of every second cycle up to 12 cycles (approximately 9 months). Each cycle is a 21 days cycle
measure: Number of Participants With Antitherapeutic Antibodies (ATA)
timeFrame: Day 1 of every 21 days cycle and at End of study (EOS) approximately 9 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: