Dose Escalation Trial of Dalotuzumab (MK-0646) in Advanced Solid Tumors and Multiple Myeloma (MK-0646-001)

NCT00701103 | Completed Phase 1 Results

• 2 other identifiers: 0646-0012007_660
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will look for the highest tolerated dose of dalotuzumab (MK-0646) given as weekly, every other week. or a every three week infusion. The hypothesis of this study is that administration of dalotuzumab as a one- to two-hour weekly, every other week, or every three week infusion in participants with advanced cancer will be generally safe and tolerated at a dose which achieves a trough concentration ≥3 μg/mL.

Conditions

Solid Tumor; Multiple Myeloma

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants Who Experienced One or More Dose-limiting Toxicities (DLTs)

  Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE 3.0). A DLT was defined as any Grade 3 or 4 toxicity. A Grade 3 toxicity was defined as severe or medically significant but not immediately life-threatening OR hospitalization or prolongation of hospitalization indicated OR disabling OR limiting self care activities of daily living. A Grade 4 toxicity was defined as: life-threatening consequences OR urgent intervention indicated. Participants were monitored for the occurrence of DLTs during the first 3 weeks of dosing with dalotuzumab.

  Up to 3 weeks

• Mean Terminal Half-life (t1/2) of Dalotuzumab

  Terminal half-life is defined as the time it takes for the blood plasma concentration of a substance to halve (plasma half-life). Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions \>1 hour in duration, an additional sample was obtained at the mid-point of the infusion. Data presented are for the harmonic mean t1/2 for dalotuzumab.

  Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion

• Area Under the Time-concentration Curve From 0 to Infinity Hours (AUC0-∞) of Dalotuzumab

  AUC0-∞ represents the total drug exposure over time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion. For infusions \>1 hour in duration, an additional sample was obtained at the mid-point of the infusion.

  Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion

• Mean Serum Clearance of Dalotuzumab

  Clearance is defined as the volume of serum from which study drug was completely removed per unit of time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions \>1 hour in duration, an additional sample was obtained at the mid-point of the infusion.

  Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion

• Mean Trough Serum Concentration (Ctrough) of Dalotuzumab

  The lowest (trough) concentration of dalotuzumab prior to the next dose of dalotuzumab was measured.

  Pre-dose immediately prior to second infusion: 168 hours for Q1W, 336 hours for Q2W and 504 hours for Q3W dosing

Secondary Outcomes (4)

• Change From Baseline in Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Expression Level H-score in Skin Samples

  Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)

• Change From Baseline in IGF-1R Protein Expression Level H-score in Tumor Samples

  Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)

• Percentage of Participants Who Developed a Serum Human-anti-humanized-antibody (HAHA) Response to Dalotuzumab

  Up to 2 years

• Percentage of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)

  Up to 2 years

Study Arms (11)

Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) intravenous (IV) infusion 1 time every 1 week (Q1W).

Drug: Dalotuzumab

Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.

Drug: Dalotuzumab

Dalotuzumab 5 mg/kg Q1W (10 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.

Drug: Dalotuzumab

Dalotuzumab 10 mg/kg Q1W (10 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.

Drug: Dalotuzumab

Dalotuzumab 10 mg/kg Q1W (20 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.

Drug: Dalotuzumab

Dalotuzumab 15 mg/kg Q1W (10 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.

Drug: Dalotuzumab

Dalotuzumab 15 mg/kg Q1W (20 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.

Drug: Dalotuzumab

Dalotuzumab 20 mg/kg Q1W (10 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.

Drug: Dalotuzumab

Dalotuzumab 20 mg/kg Q1W (20 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.

Drug: Dalotuzumab

Dalotuzumab 20 mg/kg Q2W (20 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion 1 time every 2 weeks (Q2W).

Drug: Dalotuzumab

Dalotuzumab 30 mg/kg Q3W (20 mg/mL)

EXPERIMENTAL

Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion1 time every 3 weeks (Q3W).

Drug: Dalotuzumab

Interventions

Dalotuzumab DRUG

IV infusion

Also known as: MK-0646

Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL); Dalotuzumab 10 mg/kg Q1W (10 mg/mL); Dalotuzumab 10 mg/kg Q1W (20 mg/mL); Dalotuzumab 15 mg/kg Q1W (10 mg/mL); Dalotuzumab 15 mg/kg Q1W (20 mg/mL); Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL); Dalotuzumab 20 mg/kg Q1W (10 mg/mL); Dalotuzumab 20 mg/kg Q1W (20 mg/mL); Dalotuzumab 20 mg/kg Q2W (20 mg/mL); Dalotuzumab 30 mg/kg Q3W (20 mg/mL); Dalotuzumab 5 mg/kg Q1W (10 mg/mL)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has metastatic or locally advanced solid tumor or multiple myeloma
• Tumor specimen has IGF-1R expression
• Participant agrees to use birth control throughout study

You may not qualify if:

• Participant must not be recovering from antineoplastic therapy in the last 4 weeks
• Participant has participated in a clinical trial in the last 4 weeks
• Participant has a history of heart problems such as congestive heart failure, angina, heart attack or stroke in the last 3 months
• Participant is taking growth hormone or growth hormone inhibitors
• If female, participant is pregnant or breastfeeding
• Participant is human immunodeficiency virus (HIV) positive
• Participant has a history of hepatitis B or C

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Atzori F, Tabernero J, Cervantes A, Prudkin L, Andreu J, Rodriguez-Braun E, Domingo A, Guijarro J, Gamez C, Rodon J, Di Cosimo S, Brown H, Clark J, Hardwick JS, Beckman RA, Hanley WD, Hsu K, Calvo E, Rosello S, Langdon RB, Baselga J. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2011 Oct 1;17(19):6304-12. doi: 10.1158/1078-0432.CCR-10-3336. Epub 2011 Aug 2.

  PMID: 21810918 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

dalotuzumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2008
• First Posted: June 19, 2008
• Study Start: January 12, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 8, 2018
• Results First Posted: March 21, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share