Clinical trial NCT01243762
Conditions: Neoplasms Malignant
Keywords: Colorectal cancer Solid tumors Ovarian cancer Fallopian tube cancer Primary peritoneal cancer
Sponsor: Merck Sharp & Dohme LLC
Start date: 2010-11-22; Completion date: 2013-03-25
Enrollment: 47 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is an open-label, two-part study to evaluate the safety and tolerability of combination treatment with dalotuzumab + MK-2206, dalotuzumab + MK-0752, or dalotuzumab + ridaforolimus (MK-8669). Part 1 of the study will determine the dose-limiting toxicities (DLTs) observed after administration of each of the combinations at various doses and define the maximum tolerated dose (MTD) of each combination. Part 2 of the study will assess preliminary anti-tumor activity of these combinations (at MTD) in two groups of participants with selected tumor biomarkers: one group with metastatic or recurrent platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and one group with metastatic or recurrent colorectal cancer. The dalotuzumab + ridaforolimus and dalotuzumab + MK-2206 arms will be enriched with female platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer participants. The dalotuzumab + MK-0752 arm will be enriched with metastatic or recurrent wild-type kirsten rat sarcoma (KRAS) colorectal cancer participants.

The primary hypothesis is that the DLTs observed in adult patients with locally advanced or metastatic solid tumors after administration of each of the MK-MK doublets will be dose-dependent to allow for definition of a MTD within each MK-MK doublet.

Detailed description:

Arms: arm 1: Participants in Part 1 of the study receive dalotuzumab 7.5 mg/kg intravenously (IV) weekly + MK-0752 1800 mg orally (PO) weekly in 28-day cycles for a maximum of 6 months of study therapy. arm 2: Participants in Parts 1 and 2 of the study receive dalotuzumab 10 mg/kg IV weekly + MK-0752 1800 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy. arm 3: Participants in Part 1 of the study receive dalotuzumab 10 mg/kg IV weekly + MK-2206 90 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy. arm 4: Participants in Part 1 of the study receive dalotuzumab 10 mg/kg IV weekly + MK- 2206 135 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy. arm 5: Participants in Parts 1 and 2 of the study receive dalotuzumab 10 mg/kg IV weekly + MK- 2206 150 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy. arm 6: Participants in Part 1 of the study receive dalotuzumab 10 mg/kg IV weekly + MK- 2206 200 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy. arm 7: Participants in Part 2 of the study receive dalotuzumab 10 mg/kg IV weekly + ridaforolimus 20 mg PO daily for 5 consecutive days per week in 28-day cycles for a maximum of 6 months of study therapy.
Interventions: intervention 1: dalotuzumab intervention 2: MK-0752 intervention 3: ridaforolimus intervention 4: MK-2206
Intervention descriptions: intervention 1: Administered intravenously (IV) once weekly in 28-day cycles for a maximum of 6 months of study therapy intervention 2: Administered orally (PO) weekly in 28-day cycles for a maximum of 6 months of study therapy intervention 3: Administered PO daily for 5 consecutive days per week in 28-day cycles for a maximum of 6 months of study therapy intervention 4: Administered PO weekly in 28-day cycles for a maximum of 6 months of study therapy

Protocol documents: