Phase 1 Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C

This study has been completed.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc. Identifier:
First received: April 2, 2012
Last updated: October 1, 2014
Last verified: October 2014
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.

Condition Intervention Phase
Advanced Gastrointestinal Malignancies
Drug: MLN0264
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Number of Dose-limiting toxicities (DLTs), adverse events, serious adverse events, assessment of clinical laboratory values and vital sign measurements [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 36 to 42 months ] [ Designated as safety issue: Yes ]
    To assess the safety profile, including DLTs, of MLN0264

  • Maximum Tolerated Dose (MTD) [ Time Frame: Every 3 weeks until MTD is established, approximately 12 months ] [ Designated as safety issue: No ]
    To determine the MTD of MLN0264

  • PK parameters including AUC and Cmax [ Time Frame: Cycle 1 and 2: Day 1, 2, 3, 4, 8, 15; Subsequent Cycles: Day 1, 2(Cycle 6), 3, 8(Cycle 6), 15 and End Of Study (EOS), approximately 12 months. Each cycle is a 21 days cycle ] [ Designated as safety issue: No ]
    To determine the PK profile of MLN0264

Secondary Outcome Measures:
  • Disease response rate [ Time Frame: At the completion of every second cycle upto 17 cycles (approximately 12 months). Each cycle is a 21 days cycle ] [ Designated as safety issue: No ]
    To evaluate disease response rate that may be observed with MLN0264

  • Assessment of antitherapeutic antibodies (ATA) [ Time Frame: Day 1 of every 21 days cycle and at EOS ] [ Designated as safety issue: No ]
    To evaluate immunogenicity of MLN0264 (ATA development)

Enrollment: 41
Study Start Date: June 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MLN0264 Drug: MLN0264
All patients will receive MLN0264 as a 30-minute infusion on Day 1 of each treatment cycle


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01577758

United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT01577758     History of Changes
Other Study ID Numbers: C26001  2011-002260-24 
Study First Received: April 2, 2012
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:
Phase 1,
Advanced gastrointestinal malignancies,
Guanylyl Cyclase C(GCC),
Antibody Drug Conjugate(ADC)

Additional relevant MeSH terms:
Neoplasms processed this record on April 27, 2016