Study of MLN2480 in Patients With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion in Patients With Metastatic Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01425008
First received: August 26, 2011
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

This is a phase 1, multicenter, nonrandomized, open-label, dose escalation study. The study will be conducted in 2 stages, Dose Escalation and Dose Expansion. The Dose Escalation phase will include patients with solid tumors (including melanoma) who have failed or are not candidates for standard therapies or for whom no approved therapy is available. The Dose Expansion phase will include patients with metastatic melanoma.


Condition Intervention Phase
Melanoma
Metastatic Melanoma
Solid Tumor
Drug: MLN2480
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1, Dose Escalation Study of MLN2480 in Patients With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion Phase in Patients With Metastatic Melanoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Incidence of adverse events, serious adverse events, dose-limiting adverse events within the first cycle, and deaths [ Time Frame: From first dose of study treatment to end of study visit, approximately 1 year and 30 days ] [ Designated as safety issue: Yes ]
    Safety and tolerability of MLN2480


Secondary Outcome Measures:
  • Objective response rate, duration of response, and progression-free survival [ Time Frame: Every 2 cycles after starting MLN2480 treatment, beginning on Cycle 2, Day 21 +/- 2 days, expected duration approximately 1 year ] [ Designated as safety issue: No ]
    Preliminary antitumor activity of MLN2480

  • Maximum observed concentration (Cmax), trough concentration (Ctrough), first time to maximum concentration (tmax), t1/2, renal clearance, and area under the plasma concentration-time curve (AUC) [ Time Frame: At multiple time points throughout Cycle 1 and Day 1 of Cycle 2, for approximately 23 days ] [ Designated as safety issue: No ]
    Pharmacokinetics of MLN2480

  • Inhibition of phosphorylated extracellular signal-regulated kinase (pERK) and Ki67, and Caspase-3 staining [ Time Frame: Before first dose of MLN2480 and on Day 21 ] [ Designated as safety issue: No ]
    Pharmacodynamics of MLN2480


Estimated Enrollment: 142
Study Start Date: September 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MLN2480 Drug: MLN2480
Dose Escalation Phase: patients will receive MLN2480 orally in escalating doses every other day or once weekly for three weeks of a 28-day cycle. Patients may continue treatment for additional cycles (up to 12 months) until disease progression, unacceptable toxicity, or the patient discontinues for any other reason. If it is determined that a patient would derive benefit from continued therapy beyond 12 months treatment may continue. Dose Expansion Phase: Patients will take MLN2480 at the maximum tolerated dose orally every other day or once weekly for three weeks of a 28-day cycle until disease progression, unacceptable toxicity, or the patient discontinues for any other reason. The maximum duration of treatment is 1 year unless determined that a patient would derive benefit from continued therapy beyond 12 months.

  Eligibility

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

Inclusion Criteria:

  • Informed consent
  • Male or female patients 18 years or older
  • Dose Escalation phase: Patients with solid tumors (including melanoma) who have failed or are not candidates for standard therapies of for whom no approved therapy is available
  • Dose Expansion phase: Metastatic melanoma (locally advanced or metastatic melanoma)
  • Dose Expansion phase: At least 1 measurable lesion which has not been treated previously with radiotherapy. A newly arising lesion in a previously irradiated field is acceptable
  • For patients undergoing biopsy procedures: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be within the normal range
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Adequate tissue sample from either archival formalin-fixed paraffin-embedded (FFPE) tumor tissue or new biopsy of tumor
  • Previous chemotherapy, immunotherapy, and hormone therapy must be completed at least 4 weeks prior to the administration of MLN2480 and radiation must be completed at least 3 weeks prior to the administration of MLN2480; all associated toxicity must be resolved to ≤ Grade 1
  • Expected survival time of at least 3 months in the opinion of the investigator
  • Patients who do not have hypo- or hyperthyroidism
  • Ability to swallow and retain oral medication
  • Female patients who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 3 months after the last dose of study drug or agree to practice true abstinence
  • Male patients who, even if surgically sterilized, agree to practice effective barrier contraception through 3 months after the last dose of alisertib or agree to practice true abstinence

Exclusion Criteria

  • History of any major disease that might interfere with safe protocol participation
  • Dose Expansion phase: Previous treatment with RAF or MEK inhibitors
  • Laboratory values as specified in study protocol
  • Current enrollment in any other investigational treatment study
  • Evidence of current uncontrolled cardiovascular conditions within the past 6 months
  • Prior investigational agents for malignant or non-malignant disease within 4 weeks prior to Day 1
  • Active hepatitis or human immunodeficiency virus (HIV) infection
  • Active bacterial or viral infection
  • Female patients who are pregnant or currently breastfeeding
  • Major surgery within 28 days of Day 1
  • Refractory nausea and vomiting, malabsorption, or significant bowel or stomach resection
  • Inability to comply with study requirements
  • Other unspecified reasons that, in the opinion of the investigator or Millennium, make the patient unsuitable for enrollment
  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: NCT01425008

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, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
The START Center Recruiting
San Antonio, Texas, United States, 78229
United Kingdom
Cambridge University Hospitals NHS Foundation Trust (Addenbrooke's Hospital) Recruiting
Cambridge, United Kingdom
The Royal Marsden Hospital Recruiting
London, United Kingdom
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom
Newcastle upon Tyne Hospitals Recruiting
Newcastle upon Tyne, United Kingdom
Oxford University Hospitals NHS Trust Recruiting
Oxford, United Kingdom
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: NCT01425008     History of Changes
Other Study ID Numbers: C28001, 2012-003397-16
Study First Received: August 26, 2011
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Neoplasms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on September 22, 2014