Clinical trial NCT00701103: Dose Escalation Trial of Dalotuzumab (MK-0646) in Advanced Solid Tumors and Multiple Myeloma (MK-0646-001)
Official title: An Open-Label, Dose Escalation Phase I Trial of MK-0646 Given as a Once Weekly, Every Other Week, or Every Three Week Infusion in Patients With Advanced Solid Tumors and Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Multiple Myeloma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-06-19
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Trial Duration of Treatment: Participants can be treated for up to two years if their disease has not progressed and they are not having unmanageable side effects.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants Who Experienced One or More Dose-limiting Toxicities (DLTs)
timeFrame: Up to 3 weeks
measure: Mean Terminal Half-life (t1/2) of Dalotuzumab
timeFrame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
measure: Area Under the Time-concentration Curve From 0 to Infinity Hours (AUC0-∞) of Dalotuzumab
timeFrame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
measure: Mean Serum Clearance of Dalotuzumab
timeFrame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
measure: Mean Trough Serum Concentration (Ctrough) of Dalotuzumab
timeFrame: Pre-dose immediately prior to second infusion: 168 hours for Q1W, 336 hours for Q2W and 504 hours for Q3W dosing
Secondary outcomes:
measure: Change From Baseline in Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Expression Level H-score in Skin Samples
timeFrame: Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)
measure: Change From Baseline in IGF-1R Protein Expression Level H-score in Tumor Samples
timeFrame: Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)
measure: Percentage of Participants Who Developed a Serum Human-anti-humanized-antibody (HAHA) Response to Dalotuzumab
timeFrame: Up to 2 years
measure: Percentage of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)
timeFrame: Up to 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.