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

NCT00635778 | Completed Phase 1 Results

• 2 other identifiers: 0646-002MK-0646-002
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose

  Blood samples were obtained for analysis of steady-state serum concentration of dalotuzumab at 336 hours (C336) after the first maintenance dose of dalotuzumab. The C336 of dalotuzumab after intravenous administration is presented.

  2 weeks post first maintenance dose of study drug (3 weeks post loading dose of study drug)

• Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs)

  Dose-limiting toxicities (DLT) were assessed and graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE). A DLT was defined as the occurrence of any of the following events, that were judged by the study investigator, to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever \>38.5 degrees Celsius; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity (except alopecia and inadequately treated diarrhea, nausea, and vomiting, and hyperglycemia lasting less than 5 days; and Grade 3 or greater hyperglycemia lasting for more than 5 days in spite of optimal medical management.

  The entire treatment period (Up to 18 months)

Secondary Outcomes (16)

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

  Up to 18 months post first dose of study drug

• Percent Change From Baseline in Serum Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Level at Week 1

  Baseline and Week 1

• Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer

  Prior to second and subsequent doses of study drug (Up to 1 year post-first dose)

• Percent Change From Baseline in Serum IGF-1R Protein Level at Week 5

  Baseline and Week 5

• Percent Change From Baseline in Serum IGF-1R Protein Level at Week 9

  Baseline and Week 9

Study Arms (7)

dalotuzumab 2.5/2.5 mg/kg

EXPERIMENTAL

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.

Drug: dalotuzumab

dalotuzumab 5.0/5.0 mg/kg

EXPERIMENTAL

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.

Drug: dalotuzumab

dalotuzumab 10.0/5.0 mg/kg

EXPERIMENTAL

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.

Drug: dalotuzumab

dalotuzumab 15.0/5.0mg/kg

EXPERIMENTAL

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.

Drug: dalotuzumab

dalotuzumab 20.0/5.0 mg/kg

EXPERIMENTAL

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.

Drug: dalotuzumab

dalotuzumab 15.0/10.0 mg/kg

EXPERIMENTAL

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.

Drug: dalotuzumab

dalotuzumab 15.0/15.0 mg/kg

EXPERIMENTAL

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.

Drug: dalotuzumab

Interventions

dalotuzumab DRUG

Administered as an IV infusion over one to two hours

Also known as: MK-0646

dalotuzumab 10.0/5.0 mg/kg; dalotuzumab 15.0/10.0 mg/kg; dalotuzumab 15.0/15.0 mg/kg; dalotuzumab 15.0/5.0mg/kg; dalotuzumab 2.5/2.5 mg/kg; dalotuzumab 20.0/5.0 mg/kg; dalotuzumab 5.0/5.0 mg/kg

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Interventions

dalotuzumab

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2008
• First Posted: March 14, 2008
• Study Start: August 7, 2006
• Primary Completion: November 5, 2008
• Study Completion: November 5, 2008
• Last Updated: October 9, 2018
• Results First Posted: October 9, 2018

Record last verified: 2018-02