A Dose-finding Study of Dalotuzumab in Subjects With Advanced Solid Tumors (MK-0646-002)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: dalotuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00635778

0646-002

MK-0646-002 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 7 patient groups

dalotuzumab 2.5/2.5 mg/kg

Experimental group

Description:

Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by intravenous (IV) infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.

Treatment:

Drug: dalotuzumab

dalotuzumab 5.0/5.0 mg/kg

Experimental group

Description:

Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.

Treatment:

Drug: dalotuzumab

dalotuzumab 10.0/5.0 mg/kg

Experimental group

Description:

Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.

Treatment:

Drug: dalotuzumab

dalotuzumab 15.0/5.0mg/kg

Experimental group

Description:

Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.

Treatment:

Drug: dalotuzumab

dalotuzumab 20.0/5.0 mg/kg

Experimental group

Description:

Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.

Treatment:

Drug: dalotuzumab

dalotuzumab 15.0/10.0 mg/kg

Experimental group

Description:

Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.

Treatment:

Drug: dalotuzumab

dalotuzumab 15.0/15.0 mg/kg

Experimental group

Description:

Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.

Treatment:

Drug: dalotuzumab