Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin (8669-015)

NCT00288431 | Completed Phase 1

• 2 other identifiers: 8669-015AP23573-05-107
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is designed to determine the safety, tolerability and maximum tolerated dose of Oral AP23573 in combination with Doxorubicin

Conditions

Cancer; Sarcoma

Keywords

cancer; sarcoma

Outcome Measures

Primary Outcomes (1)

• determine the maximum tolerated dose (MTD) of oral AP23573 in combination with doxorubicin

  Duration of study

Secondary Outcomes (3)

• Describe the antitumor activity of the study drug combination for each dosing schedule

  Duration of study

• examine the pharmacokinetics of oral AP23573 and doxorubicin when given in combination

  Duration of study

• Examine pharmacodynamic characteristics of AP23573 for those patients enrolled into the expanded MTD cohorts only

  Duration of study

Study Arms (1)

1

EXPERIMENTAL

Different schedules and routes of administration of AP23573 will be examined. For each schedule, AP23573 + Doxorubicin will be co-administered on Day 1 of a 3-week cycle. AP23573 will be given orally and will range in dose from 10-30 mg per dose.

Drug: ridaforolimus; Drug: Doxorubicin

Interventions

ridaforolimus DRUG

Different schedules and routes of administration of AP23573 will be examined. For each schedule, AP23573 + Doxorubicin will be co-administered on Day 1 of a 3-week cycle. AP23573 will be given orally and will range in dose from 10-30 mg per dose.

Also known as: deforolimus, AP23573, MK-8669, ridaforolimus was also known as deforolimus until May 2009

1

Doxorubicin DRUG

administered at 60 mg/m2 intravenously every 3 weeks

1

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years with a histological/cytological diagnosis of advanced tumor, preferentially breast, sarcoma, ovarian, endometrial or other tumor types for which treatment with anthracycline therapy is indicated
• Prior cumulative doxorubicin exposure less than 400 mg/m2
• An ECOG performance status of 0 or 1
• Adequate cardiovascular function
• Measurable disease according to modified RECIST criteria
• Adequate hematological, renal and hepatic functions
• Able to understand and give voluntary written informed consent

You may not qualify if:

• Women who are pregnant or lactating
• Presence of active brain metastases. Patients with treated brain metastases will be eligible if they are on a stable dose of corticosteroids or are without change in brain disease status for at least 4 weeks following related therapy (e.g., whole brain radiation, surgery)
• Prior treatment with CCI-779, rapamycin, or any other mTOR inhibitor
• Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy, biological response modifiers, signal transduction inhibitors, etc) within 4 weeks prior to the first dose of AP23573; the interval is ≥ 2 weeks for signal transduction inhibitors with a half-life known to be \<24 hours, and is ≥ 6 weeks for nitrosourea or mitomycin. Exception: Concurrent treatment with LHRH agonists is allowed for patients with prostate cancer.
• Ongoing toxicity associated with prior anticancer therapy other than alopecia and ≤ Grade 1 peripheral neuropathy by NCI toxicity criteria
• Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ)
• Known or suspected hypersensitivity to any excipient contained in the study drug
• Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
• Significant uncontrolled cardiovascular disease
• Any active infection requiring prescribed intervention
• Any other concurrent illness which, in the opinion of the investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the study drug
• Any pre-existing malabsorption syndrome, irritable bowel syndrome or other clinical situation which could affect oral absorption
• Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug
• Concurrent treatment with medications that induce or inhibit cytochrome P450 (CYP3A)
• Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of AP23573

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Ariad Pharmaceuticals: collaborator

MeSH Terms

Conditions

Neoplasms; Sarcoma

Interventions

ridaforolimus; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2006
• First Posted: February 8, 2006
• Study Start: February 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: July 22, 2015

Record last verified: 2015-07