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Dose Escalation Study of MLN0128 in Subjects With Advanced Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01058707
First received: January 27, 2010
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

This is a Phase I, Open Label, Dose Escalation Study of Oral Administration of Single Agent MLN0128 in Subjects with Advanced Malignancies Followed by an Expansion in Subjects with renal cell carcinoma, endometrial cancer or urothelial cancer who have measurable disease


Condition Intervention Phase
Advanced Solid Malignancies
Drug: MLN0128
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open Label, Dose Escalation Study of Oral Administration of Single Agent INK128 in Subjects With Advanced Malignancies Followed by an Expansion in Subjects With Measurable Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD)and number of Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1: Day 1, 2, 8, 15, and 22 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of orally administered single agent MLN0128 [ Time Frame: At screening/baseline; Cycle 1: Day 1, 2, 8, 15, and 22; Cycle 2: Day 1, 8, 15, and 22; Cycle 3 and 4: Day 1, 15, and 22; Cycle 5 and thereafter : Day1; and at termination visit ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • PK parameters including AUC, Cmax, Cmin, Tmax and t1/2 [ Time Frame: Cycle 1: Day 1, 2 and any day of Days 8-15; Cycle 2: Day 1 and 2 ] [ Designated as safety issue: No ]
  • Pharmacodynamics (PD) Assessment of MLN0128 [ Time Frame: Cycle 1 Day 1, 2, 8, 15, and 22; Cycle 2 Day 1, 8, 15, 22; Cycles 3&4 Day 1 & 15; Cycle 5 and Onward Day 1, and at termination visit ] [ Designated as safety issue: No ]
  • To evaluate preliminary anti-tumor activity of MLN0128 [ Time Frame: At screening and thereafter every 2 cycles of treatment. Each cycle is a 28 day cycle ] [ Designated as safety issue: No ]

Estimated Enrollment: 190
Study Start Date: January 2010
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MLN0128 Drug: MLN0128
MLN0128 will be administered orally with one of 4 different dosing schedules - once daily (QD), once weekly (QW), once daily for 3 days on;4 days off repeated each week (QDX3d QW), and once daily for 5 days on;2 days off repeated each week (QDX5d QW)

  Eligibility

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

Inclusion Criteria:

  • Voluntary written consent
  • Locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Ability to swallow oral medications
  • Life expectancy of ≥6 months
  • For women of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to the first study drug administration and use of physician-approved method of birth control from 30 days prior to 30 days following the last study drug administration
  • Male subjects must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration
  • Clinical laboratory values as specified in the protocol

Additionally, to be eligible for the Dose Expansion portion of the study:

  • Subjects must have a pathologic diagnosis of advanced or recurrent endometrial adenocarcinoma and must have failed at least 1 prior line of standard chemotherapy
  • Subjects must have a pathologic diagnosis of advanced/metastatic urothelial cancer (carcinoma of the bladder, ureter, and/or renal pelvis) and must have failed at least 1 line of prior therapy in the metastatic/unresectable setting
  • Subjects must have a pathologic diagnosis of advanced renal cell carcinoma (RCC), with histological or cytological confirmation of RCC with a clear cell component, and must have failed at least 1 prior line of anti-VEGF therapy (including but not limited to sunitinib, and/or sorafenib, and/or bevacizumab and/or pazopanib, and/or axitinib) and must not have received prior therapy with a TORC1 inhibitor (such as temsirolimus or everolimus); or
  • Subjects must have a pathologic diagnosis of advanced renal cell carcinoma (RCC) and must have progressed on treatment with a TORC1 inhibitor (such as temsirolimus or everolimus).

Exclusion Criteria:

  • Diagnosis of primary brain tumor
  • Have received prior cancer or other investigational therapy within 2 weeks prior to the first administration of study drug
  • Known impaired cardiac function or clinically significant cardiac disease
  • Known treatment with systemic corticosteroid within one week prior to the first administration of study drug
  • Diabetes mellitus
  • HIV infection
  • Known active cardiovascular disease condition as specified in protocol
  • Failed to recover from the reversible effects of prior anticancer therapies
  • Pregnancy (positive serum or urine pregnancy test) or breast feeding
  • Malabsorption due to prior gastrointestinal (GI) surgery, GI disease
  • Other clinically significant co-morbidities 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 ClinicalTrials.gov identifier: NCT01058707

Contacts
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-877-674-3784 medical@mlnm.com

Locations
United States, Arizona
Recruiting
Scottsdale, Arizona, United States, 85258
United States, Indiana
Recruiting
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02115
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
Recruiting
Nashville, Tennessee, United States, 37232
Spain
Recruiting
Barcelona, Spain
Recruiting
Valencia, Spain
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01058707     History of Changes
Other Study ID Numbers: INK128-001, 2009-017284-42
Study First Received: January 27, 2010
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration
Spain: Spanish Medicines and Healthcare Products Agency(AEMPS)

Keywords provided by Millennium Pharmaceuticals, Inc.:
Solid tumors, MLN0128, TORC1/2 inhibitors

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014