NCT00694356

Study of Dalotuzumab (MK-0646) in Adults With Solid Tumors (MK-0646-009)

Completed Phase 1 Results posted Last updated 8 August 2018

What this trial tests

Phase 1 trial testing Dalotuzumab in Neoplasm in 15 participants. Completed in 28 April 2009.

Timeline

4 August 2008

Primary endpoint
18 March 2009

28 April 2009

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	15
Start date	4 August 2008
Primary completion	18 March 2009
Estimated completion	28 April 2009

Drugs / interventions tested

• Dalotuzumab — full drug profile →

Conditions studied

• Neoplasm — all drugs for Neoplasm →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

20 and older, any sex, with Neoplasm. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) Primary · Cycle 1 (Up to 4 weeks)

Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. DLTs were defined as the occurrence of any of the following events when judged to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever \>38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except alopecia and inadequately treated diarrhea, nausea and vomiting. The number of participants who experienced a DLT is presented.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	0
Dalotuzumab 10 mg/kg	0
Dalotuzumab 15 mg/kg/7.5 mg/kg	0

Number of Participants Who Experienced an Adverse Event (AE) Primary · Up to 30 days after last dose of study treatment (Up to 101 days)

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	3
Dalotuzumab 10 mg/kg	6
Dalotuzumab 15 mg/kg/7.5 mg/kg	6

Number of Participants Who Discontinued Study Treatment Due to an AE Primary · Up to 71 days

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	1
Dalotuzumab 10 mg/kg	0
Dalotuzumab 15 mg/kg/7.5 mg/kg	0

Maximum Plasma Concentration (Cmax) of Dalotuzumab Secondary · Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose

Cmax was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	85.60	± 6.94
Dalotuzumab 10 mg/kg	161.78	± 23.02
Dalotuzumab 15 mg/kg/7.5 mg/kg	244.05	± 11.57

Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞) of Dalotuzumab Secondary · Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose

AUC0-∞ was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	11.72	1.0 – 1.0
Dalotuzumab 10 mg/kg	21.71	1.0 – 5.0
Dalotuzumab 15 mg/kg/7.5 mg/kg	38.99	1.0 – 1.0

Time to Cmax (Tmax) of Dalotuzumab Secondary · Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose

Tmax was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	1.0	1.0 – 1.0
Dalotuzumab 10 mg/kg	3.0	1.0 – 5.0
Dalotuzumab 15 mg/kg/7.5 mg/kg	1.0	1.0 – 1.0

Apparent Terminal Half-life (t1/2) of Dalotuzumab Secondary · Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose

t1/2 was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	129.85	1.0 – 1.0
Dalotuzumab 10 mg/kg	110.36	1.0 – 5.0
Dalotuzumab 15 mg/kg/7.5 mg/kg	167.09	1.0 – 1.0

Clearance (CL) of Dalotuzumab Secondary · Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose

CL of dalotuzumab was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	0.0071	± 10.06
Dalotuzumab 10 mg/kg	0.0077	± 37.64
Dalotuzumab 15 mg/kg/7.5 mg/kg	0.0064	± 21.27

Steady State Volume of Distribution (Vss) of Dalotuzumab Secondary · Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose

Vss was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	0.0776	± 17.46
Dalotuzumab 10 mg/kg	0.0740	± 24.10
Dalotuzumab 15 mg/kg/7.5 mg/kg	0.0924	± 16.74

Number of Participants Who Developed a Human Anti-Humanized Antibody (HAHA) Response to Dalotuzumab Secondary · Cycle 1: predose on Days 1, 8, 15, and 22; Cycles 2 and 3: predose on Day 1; 4 weeks after last dose of study drug

Formation of HAHAs may block efficacy by substantially increasing the clearance of dalotuzumab and limit the possibility of future dalotuzumab therapy. The occurrence of HAHAs in the sera of dalotuzumab treated participants at any of the serum collection times was assessed.

Group	Value	95% CI
Dalotuzumab 5 mg/kg	0
Dalotuzumab 10 mg/kg	0
Dalotuzumab 15 mg/kg/7.5 mg/kg	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 30 days after last dose of study treatment (Up to 101 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dalotuzumab 5 mg/kg

Serious: 0/3 (0%)

Deaths: —

Dalotuzumab 10 mg/kg

Serious: 1/6 (17%)

Deaths: —

Dalotuzumab 15 mg/kg/7.5 mg/kg

Serious: 0/6 (0%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Dalotuzumab 5 mg/kg	Dalotuzumab 10 mg/kg	Dalotuzumab 15 mg/kg/7.5 m…
Anorexia	Metabolism and nutrition disorders	—	—	—

Other adverse events (61 terms — click to expand)

Reaction	System	Dalotuzumab 5 mg/kg	Dalotuzumab 10 mg/kg	Dalotuzumab 15 mg/kg/7.5 m…
Blood lactate dehydrogenase increased	Investigations	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Weight decreased	Investigations	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Blood urea increased	Investigations	—	—	—
CD4 lymphocytes decreased	Investigations	—	—	—
International normalised ratio increased	Investigations	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—
Somnolence	Nervous system disorders	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—
Ear congestion	Ear and labyrinth disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—
Gingival pain	Gastrointestinal disorders	—	—	—
Melaena	Gastrointestinal disorders	—	—	—
Pyrexia	General disorders	—	—	—
Hyperbilirubinaemia	Hepatobiliary disorders	—	—	—
Drug hypersensitivity	Immune system disorders	—	—	—
Influenza	Infections and infestations	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Activated partial thromboplastin time shortened	Investigations	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—
Blood glucose increased	Investigations	—	—	—
Blood urine present	Investigations	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—
International normalised ratio decreased	Investigations	—	—	—
Prothrombin time shortened	Investigations	—	—	—

Most-reported serious reactions: Anorexia.

Data from ClinicalTrials.gov NCT00694356 adverse events section.

Sponsor's own description

This clinical study evaluates the safety, tolerability, pharmacokinetics, and immunogenicity of dalotuzumab (MK-0646) in participants with relapsed or refractory locally advanced or metastatic solid tumors using once weekly and once every other week dose infusion regimens.

The primary study hypothesis is that administration of dalotuzumab as a once weekly and an every other week infusion will be generally safe and well tolerated

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Therapeutic Approaches Targeting PAX3-FOXO1 and Its Regulatory and Transcriptional Pathways in Rhabdomyosarcoma.
   Nguyen TH, Barr FG. · · 2018 · cited 54× · PMID 30373318 · DOI 10.3390/molecules23112798