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

NCT ID: NCT01425008

Last Updated: 2020-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 149 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-15
• Study Completion Date: 2018-10-16

Brief Summary

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 participants 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 participants with metastatic melanoma.

Conditions

Melanoma; Metastatic Melanoma; Solid Tumor; Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MLN2480

Group Type: EXPERIMENTAL

MLN2480

Intervention Type: DRUG

Dose Escalation Phase: participants will receive MLN2480 orally in escalating doses every other day or once weekly for three weeks of a 28-day cycle. Participants may continue treatment for additional cycles (up to 12 months) until disease progression, unacceptable toxicity, or the participant discontinues for any other reason. If it is determined that a participant would derive benefit from continued therapy beyond 12 months treatment may continue. Dose Expansion Phase: Participants 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 participant discontinues for any other reason. The maximum duration of treatment is 1 year unless determined that a participant would derive benefit from continued therapy beyond 12 months.

Interventions

MLN2480

Dose Escalation Phase: participants will receive MLN2480 orally in escalating doses every other day or once weekly for three weeks of a 28-day cycle. Participants may continue treatment for additional cycles (up to 12 months) until disease progression, unacceptable toxicity, or the participant discontinues for any other reason. If it is determined that a participant would derive benefit from continued therapy beyond 12 months treatment may continue. Dose Expansion Phase: Participants 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 participant discontinues for any other reason. The maximum duration of treatment is 1 year unless determined that a participant would derive benefit from continued therapy beyond 12 months.

Intervention Type: DRUG

Other Intervention Names

TAK-580

Eligibility Criteria

Inclusion Criteria

1. Informed consent.

2. Male or female participants 18 years or older.

3. Dose Escalation phase: Participants with solid tumors (including melanoma) who have failed or are not candidates for standard therapies of for whom no approved therapy is available.

4. Dose Expansion phase: Metastatic melanoma (locally advanced or metastatic melanoma).

5. 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.

6. For participants undergoing biopsy procedures: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be within the normal range.

7. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 1.

8. Adequate tissue sample from either archival formalin-fixed paraffin-embedded (FFPE) tumor tissue or new biopsy of tumor.

9. 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.

10. Expected survival time of at least 3 months in the opinion of the investigator.

11. Participants who do not have hypo- or hyperthyroidism.

12. Ability to swallow and retain oral medication.

13. Female participants who are postmenopausal 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.

14. Male participants 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

1. History of any major disease that might interfere with safe protocol participation.

2. Dose Expansion phase: Previous treatment with RAF or MEK inhibitors.

3. Laboratory values as specified in study protocol.

4. Current enrollment in any other investigational treatment study.

5. Evidence of current uncontrolled cardiovascular conditions within the past 6 months.

6. Prior investigational agents for malignant or non-malignant disease within 4 weeks prior to Day 1.

7. Active hepatitis or human immunodeficiency virus (HIV) infection.

8. Active bacterial or viral infection.

9. Female participants who are pregnant or currently breastfeeding.

10. Major surgery within 28 days of Day 1.

11. Refractory nausea and vomiting, malabsorption, or significant bowel or stomach resection.

12. Inability to comply with study requirements.

13. Other unspecified reasons that, in the opinion of the investigator or Millennium, make the participant unsuitable for enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

San Francisco, California, United States

Denver, Colorado, United States

Augusta, Georgia, United States

Indianapolis, Indiana, United States

New York, New York, United States

Easton, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

San Antonio, Texas, United States

Lakewood, Washington, United States

Bristol, Avon, United Kingdom

Cambridge, Cambridgeshire, United Kingdom

Chelmsford, Essex, United Kingdom

London, Greater London, United Kingdom

Manchester, Greater Manchester, United Kingdom

Oxford, Oxfordshire, United Kingdom

Newcastle upon Tyne, Tyne & Wear, United Kingdom

Countries

United States; United Kingdom

References

Rasco DW, Medina T, Corrie P, Pavlick AC, Middleton MR, Lorigan P, Hebert C, Plummer R, Larkin J, Agarwala SS, Daud AI, Qiu J, Bozon V, Kneissl M, Barry E, Olszanski AJ. Phase 1 study of the pan-RAF inhibitor tovorafenib in patients with advanced solid tumors followed by dose expansion in patients with metastatic melanoma. Cancer Chemother Pharmacol. 2023 Jul;92(1):15-28. doi: 10.1007/s00280-023-04544-5. Epub 2023 May 23.

Reference Type: DERIVED

PMID: 37219686 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2012-003397-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1164-7508

Identifier Type: REGISTRY

Identifier Source: secondary_id

13/SC/0007

Identifier Type: REGISTRY

Identifier Source: secondary_id

C28001

Identifier Type: -

Identifier Source: org_study_id