Study of Oral Ridaforolimus (AP23573, MK-8669) to Treat Patients With Refractory or Advanced Malignancies (MK-8669-016 AM4)(COMPLETED)

NCT00112372 | Completed Phase 1

• 2 other identifiers: 8669-016AP23573-05-106
• Study Type: interventional
• Target: 147
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this current phase I trial is to study the safety and tolerability of an orally administered dosage form of ridaforolimus. This will be accomplished by an ascending dose study of several dosage regimens in patients with advanced malignancies.

Conditions

Cancer

Keywords

unresectable; metastatic; cancer; recurrent; malignancies; progressive

Outcome Measures

Primary Outcomes (5)

• Maximum Tolerated Dose (MTD) of Ridaforolimus When Administered Orally as an Enteric or Film Coated Tablet to Patients With Progressive or Recurrent Malignancies

  Cycle 1 (Day 1 to Day 28)

• Length of Exposure to Ridaforolimus

  Complete duration of study (up to approximately 42 months)

• Cumulative Dose of Ridaforolimus

  Complete duration of study (up to approximately 42 months)

• Number of Participants With Dose Limiting Toxicity (DLT)

  Cycle 1 (Day 1 to Day 28)

• Efficacy (Clinical Benefit Rate [CBR]) of Ridaforolimus in Advanced Sarcoma

  Complete duration of study (up to approximately 42 months)

Secondary Outcomes (7)

• Area Under the Curve (AUC [0-infinity]) of Ridaforolimus Administered at Different Doses and Regimens

  Cycle 1: Days 1 & 15 or 21 (depending on dosing regimen) + Cycle 2 Day 1

• Maximum Concentration (Cmax) of Ridaforolimus Administered at Different Doses and Regimens

  Cycle 1: Days 1 & 15 or 21 (depending on dosing regimen) + Cycle 2 Day 1

• Time at Which Cmax is Reached (Tmax) at Different Doses and Regimens of Ridaforolimus

  Cycle 1: Days 1 & 15 or 21 (depending on dosing regimen) + Cycle 2 Day 1

• Apparent Terminal Half-Life (t½) of Ridaforolimus

  Cycle 1: Days 1 & 15 or 21 (depending on dosing regimen) + Cycle 2 Day 1

• Relative Phospho-4E-BP1 (p-4E-BP1) Levels as a Function of Dose

  Screening, Cycle 1 Days 1, 2, 11, 15, 16, 22 + Cycle 2 Day 1 or Screening, Cycle 1 Days 1, 2, 11, 21 + Cycle 2 Day 1 (depending on dosing regimen)

Study Arms (1)

Ridaforolimus

EXPERIMENTAL

10 mg tablet of ridaforolimus administered orally according to one of several different dosing regimens for a four-week treatment cycle.

Drug: Ridaforolimus

Interventions

Ridaforolimus DRUG

10 mg tablet of ridaforolimus administered orally according to one of several different dosing regimens for a four-week treatment cycle.

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

Ridaforolimus

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥18 years of age.
• Patients with a histological/cytological diagnosis of unresectable or metastatic cancer that is refractory to standard therapies or for which no standard therapy exists.
• Patients must must have measurable or nonmeasurable lesions assessable using an appropriate radiographical procedure (e.g., computed tomography (CT) or magnetic resonance imaging (MRI) scans).
• Fertile male or female patients who agree to use approved barrier methods of contraception (non hormonal methods).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Adequate renal and hepatic function, defined as: \*Total serum bilirubin ≤ 2 x upper limit of normal (ULN) for the institution; \* (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 x ULN for the institution (≤ 5 x if due to hepatic metastases); \*Serum albumin ≥ 2 g/dL; Serum creatinine ≤ 2 x ULN for the institution
• Adequate bone marrow function, defined as: \* absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; \*Platelet count ≥ 100 x 10\^9/L
• Serum cholesterol \< 350 mg/dL and triglycerides \< 400 mg/dL.
• Anticipated life expectancy of ≥ 3 months.
• Able to give and understand a written informed consent.
• For the Phase IIa segment, patients must meet the following additional criteria:
• Patients with a histological/cytological diagnosis of metastatic and/or
• unresectable sarcoma within one of the following histological subgroups:
• Bone sarcomas
• Leiomyosarcomas

You may not qualify if:

• Patients with active central nervous system (CNS) metastases or leptomeningeal disease, not controlled by prior surgery or radiotherapy.
• Prior therapy with rapamycin, rapamycin analogs, or known sensitivity to these agents.
• Prior anticancer treatment, standard or experimental, within 4 weeks prior to the first dose of ridaforolimus (except luteinizing hormone releasing hormone (LH-RH) agonists); 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.
• Concomitant treatment with medications that induce, inhibit, or are
• metabolized by cytochrome P450 (CYP3A). Patients should be off these medications 2 weeks prior to the first dose of ridaforolimus.
• Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of ≤ grade 1 by National Cancer Institute (NCI) Terminology Criteria and alopecia).
• Another primary malignancy within the past three years (except in situ carcinoma).
• 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.
• Active infection requiring systemic therapy.
• Women who are pregnant or lactating.
• Known human immunodeficiency virus (HIV) infection .
• Other life-threatening illness, any medical condition, or organ system dysfunction, which, in the opinion of the Investigator and Sponsor, would either compromise the patient's safety or interfere with evaluation of the safety of ridaforolimus, or could interfere with the absorption of the oral study drug.
• Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug.

Sponsors & Collaborators

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

Related Publications (2)

• Mita MM, Poplin E, Britten CD, Tap WD, Rubin EH, Scott BB, Berk L, Rivera VM, Loewy JW, Dodion P, Haluska F, Sarantopoulos J, Mita A, Tolcher A. Phase I/IIa trial of the mammalian target of rapamycin inhibitor ridaforolimus (AP23573; MK-8669) administered orally in patients with refractory or advanced malignancies and sarcoma. Ann Oncol. 2013 Apr;24(4):1104-11. doi: 10.1093/annonc/mds602. Epub 2012 Dec 4.

  PMID: 23211938 RESULT

• Chawla SP, Staddon AP, Baker LH, Schuetze SM, Tolcher AW, D'Amato GZ, Blay JY, Mita MM, Sankhala KK, Berk L, Rivera VM, Clackson T, Loewy JW, Haluska FG, Demetri GD. Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas. J Clin Oncol. 2012 Jan 1;30(1):78-84. doi: 10.1200/JCO.2011.35.6329. Epub 2011 Nov 7.

  PMID: 22067397 DERIVED

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Recurrence

Interventions

ridaforolimus

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Frank Haluska, M.D.

  Ariad Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 2, 2005
• First Posted: June 3, 2005
• Study Start: May 1, 2005
• Primary Completion: December 1, 2008
• Study Completion: March 1, 2009
• Last Updated: February 12, 2015

Record last verified: 2015-02