Clinical trial NCT00635778: A Dose-finding Study of Dalotuzumab in Subjects With Advanced Solid Tumors (MK-0646-002)
Official title: An Open-Label, Dose Escalation Phase I Trial of MK-0646 Given as a One to Two Hour Every Other Week Infusion in Patients With Relapsed or Refractory Locally Advanced or Metastatic Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-03-14
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study determined the recommended Phase 2 loading and maintenance doses and dose schedules for administering dalotuzumab using dose-limiting toxicities (DLTs) observed during the entire treatment period (Up to 18 months). The primary hypothesis of the study was that administration of dalotuzumab as an every other week infusion in participants with relapsed or refractory locally advanced or metastatic cancers associated with a high frequency of insulin-like growth factor receptor type 1(IGF-1R) overexpression will be generally safe and well tolerated to permit further study and achieve a constant clearance and a minimum trough concentration of 3 µg/mL.

Detailed description: The study consisted of 3 parts. In Part 1 the loading dose was escalated while the maintenance dose was kept constant. In Part 2 the loading dose was kept constant while the maintenance dose was escalated. In Part 3 the recommended phase 2 loading and maintenance doses and schedule were administered to an expanded cohort to explore safety and efficacy of dalotuzumab.

Eligibility criteria: Inclusion Criteria:

* Males and females with advanced solid tumors who have failed to respond to standard therapy, ages 18 years and older, with adequate organ function

Exclusion Criteria:

* Participant is using growth hormones or growth hormone inhibitors
* Participant is known to be allergic to components of the drug or similar drugs (e.g. monoclonal antibodies such as rituximab or biological therapies such as immunoglobulin G
* Participant has had chemotherapy, radiotherapy, or biological therapy within 4-6 weeks of entering the study or has not recovered from previous therapy
* Participant is taking part in or has taken part in a study of an investigational compound or device within 30 days of their first dose of study drug
* Participant has an active Central Nervous System metastases and/or carcinomatous meningitis. However, a participant who has completed a course of therapy and is clinically stable may be able to participate
* Participant is pregnant or breastfeeding
* Participant is human immunodeficiency virus (HIV) positive
* Participant has a history of Hepatitis B or C
* Participant has symptomatic ascites or pleural effusion. However, if the participant has received treatment and is stable, they may be able to participate
* Female participant plans to become pregnant or a male participant who plans to impregnate their partner during the time the study is ongoing

Primary outcomes:
measure: Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose
timeFrame: 2 weeks post first maintenance dose of study drug (3 weeks post loading dose of study drug)
measure: Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs)
timeFrame: The entire treatment period (Up to 18 months)
Secondary outcomes:
measure: Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)
timeFrame: Up to 18 months post first dose of study drug
measure: Percent Change From Baseline in Serum Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Level at Week 1
timeFrame: Baseline and Week 1
measure: Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer
timeFrame: Prior to second and subsequent doses of study drug (Up to 1 year post-first dose)
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 5
timeFrame: Baseline and Week 5
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 9
timeFrame: Baseline and Week 9
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 13
timeFrame: Baseline and Week 13
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 17
timeFrame: Baseline and Week 17
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 21
timeFrame: Baseline and Week 21
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 25
timeFrame: Baseline and Week 25
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 29
timeFrame: Baseline and Week 29
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 33
timeFrame: Baseline and Week 33
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 37
timeFrame: Baseline and Week 37
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 41
timeFrame: Baseline and Week 41
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 45
timeFrame: Baseline and Week 45
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 49
timeFrame: Baseline and Week 49
measure: Percent Change From Baseline in Serum IGF-1R Protein Level at Week 53
timeFrame: Baseline and Week 53
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: