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CancerPhase 1NCT00112372

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

A Phase 1 study testing Ridaforolimus in people with Cancer, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer
What is being tested?
Ridaforolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
147 participants
Where
No sites listed yet
Study dates
May 2005to Mar 2009
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Liposarcomas
  • Presence of at least one measurable lesion that:
  • Can be accurately measured in at least one dimension with longest diameter ≥20 mm using conventional techniques or ≥10 mm with spiral CT scan (or otherwise at least twice the reconstruction interval for CT or MRI scans).
  • Previously irradiated lesions may be considered to be measurable provided: 1) there has been documented progression of the lesion(s) since completion of radiotherapy, and 2) the criteria for measurability as outlined above are met.
  • ECOG performance status ≤1

Who cannot join

  • 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).
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  • 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.
  • Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within the last 3 to 4 weeks prior to the first dose of ridaforolimus.

About this study

Official title: A Phase I/IIa, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability and Maximum Tolerated Dose of AP23573 When Administered Orally in Patients With Refractory or Advanced Malignancies

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.

Read the detailed description

The advent of oral anticancer therapy has created a means to reduce dependency on a system for treating cancer that relies on hospital-based services to administer treatment. While known disadvantages of oral therapies such as potential variable absorption, unpredictable bioavailability and sometimes poor patient compliance pose challenges, the use of orally administered compounds permits investigation of alternative or varied dose regimens, which may ultimately enhance overall patient care.

Ridaforolimus is currently being studied in phase 1 and phase II clinical trials in patients with advanced cancers. Thus far, these trials have demonstrated that ridaforolimus has a favorable safety profile and possesses anticancer activity when administered as a 30-minute intravenous (IV) infusion daily x 5 every-two-weeks or on a weekly schedule. 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
Being tested
Ridaforolimus
Keywords
unresectable, metastatic, cancer, recurrent, malignancies, progressive
Medical subject headings
Neoplasms, Neoplasm Metastasis, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RidaforolimusDrug

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

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

Study groups in NCT00112372
Study groupRoleWhat they receive
RidaforolimusExperimental10 mg tablet of ridaforolimus administered orally according to one of several different dosing regimens for a four-week treatment cycle.
Receives: Drug: Ridaforolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Cycle 1 (Day 1 to Day 28)

  2. Length of Exposure to Ridaforolimus

    Measured: Complete duration of study (up to approximately 42 months)

  3. Cumulative Dose of Ridaforolimus

    Measured: Complete duration of study (up to approximately 42 months)

  4. Number of Participants With Dose Limiting Toxicity (DLT)

    Measured: Cycle 1 (Day 1 to Day 28)

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

    Measured: Complete duration of study (up to approximately 42 months)

Secondary outcomes (7)

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

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

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

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

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

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

  4. Apparent Terminal Half-Life (t½) of Ridaforolimus

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

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

    Measured: 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)

  6. Plasma Partitioning

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

  7. Efficacy (Antitumor Activity, as Measured by CBR) of the Study Drug Regimens

    Measured: Complete duration of study (up to approximately 42 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2005 (estimated)
  2. Study startMay 2005
  3. Primary completionDec 2008
  4. Study completionMar 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
147 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00112372
Sponsor's protocol ID
8669-016
Other IDs
AP23573-05-106
Status last verified
Feb 2015
First submitted
2 Jun 2005
Last updated
12 Feb 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 23211938

  • 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.

    PubMed 22067397

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ridaforolimus in people with Cancer, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of Ridaforolimus When Administered Orally as an Enteric or Film Coated Tablet to Patients With Progressive or Recurrent Malignancies (time frame: Cycle 1 (Day 1 to Day 28)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00112372, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2015.

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