Ridaforolimus and Vorinostat in Treating Patients With Advanced Solid Tumors or Lymphoma

NCT01169532 | Completed Phase 1 Results DMC

• 2 other identifiers: 09-034NCI-2010-01907
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of giving ridaforolimus and vorinostat together in treating patients with advanced solid tumors or lymphoma. Giving ridaforolimus in combination with vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  MTD denoted as the highest dose at which no more than one of six patients experienced a dose limiting toxicity (DLT), and expanded to a total of 12 patients. Any drug-related grade 3 or 4 toxicity occurring during the first three weeks of treatment (except nausea, vomiting, diarrhea, serum lipid elevation, or transient electrolyte abnormality that resolved to a grade of 0-2 with medical management) was considered a dose limiting toxicity (DLT). Assessed by National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 4.0.

  First 3 weeks of treatment

Secondary Outcomes (2)

• Progression Free Survival

  1 year

• Overall Survival

  1 year

Study Arms (1)

Treatment (ridaforolimus and vorinostat)

EXPERIMENTAL

Patients receive ridaforolimus PO once daily on days 1-5 and vorinostat PO twice daily on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: ridaforolimus; Drug: vorinostat; Procedure: biopsy; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

ridaforolimus DRUG

Given PO

Also known as: AP23573, deforolimus, MK8669

Treatment (ridaforolimus and vorinostat)

vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Treatment (ridaforolimus and vorinostat)

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Treatment (ridaforolimus and vorinostat)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (ridaforolimus and vorinostat)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (ridaforolimus and vorinostat)

Eligibility Criteria

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

You may qualify if:

• Histological or cytological confirmation of a solid, malignant tumor or lymphoma that is refractory to standard therapies or for which no standard therapies exist
• Patients must have received at least one prior systemic therapy
• Measureable disease by RECIST v 1.1
• ECOG PS 0 or 1
• ANC \>= 1500/uL
• Hgb \>= 9 g/dL
• Platelets \>= 100,000/uL
• AST/SGOT and ALT/SGPT =\< 2.5 x upper limit of normal (ULN) or =\< 5.0 x ULN in patients with liver metastases
• Total Bilirubin =\< 1.5 times ULN
• Creatinine =\< 2.0 mg/dL or Creatinine Clearance (calculated or 24 hour urine) \>= 50 ml/min
• Female patients of childbearing potential must have a negative serum or urine pregnancy test =\< 21 days of study enrollment and agree to use an effective method of contraception for the duration of the study
• Ability to understand and willingness to sign written informed consent

You may not qualify if:

• Prior anti-cancer treatment with either an mTOR inhibitor (i.e. temsirolimus, everolimus), or an HDAC inhibitor (i.e. Vorinostat)
• Patients who have received bevacizumab =\< 6 weeks prior to day 1 of study treatment; patients who have received other chemotherapy, immunotherapy, or radiotherapy =\< 3 weeks prior to day 1 of study treatment or those who have not recovered from acute adverse events due to agents administered \>= 3 weeks earlier; for patients receiving targeted therapy, treatment must be discontinued at least five half-lives prior to initiation of day 1 of study treatment
• Patients who have taken valproic acid =\< 2 weeks of study enrollment; valproic acid is another HDAC inhibitor
• Patients who are pregnant, plan to become pregnant, or are breastfeeding
• History of gastrointestinal bleeding within1 month of enrollment
• Serum cholesterol \>= 350 mg/dL or serum triglycerides \>= 400 mg/d
• Poorly controlled Type 1 or 2 diabetes, defined as hemoglobin A1C greater than 8% or a fasting glucose of \> 160 mg/dL
• Active infection requiring antibiotics
• Anaphylactic reaction to macrolide antibiotics, Tween 80 (polysorbate 80)
• Patients who are not adequately recovered from a prior surgical procedure or major surgical procedure within 2 weeks prior to the first dose of study drug
• Myocardial infarction of unstable angina within 3 months of study entry
• NY Heart Association class III or IV congestive heart failure
• Known active parenchymal brain metastases; patients who have had brain metastases resected, or have received radiation therapy ending \> 4 weeks prior to study entry are eligible if they meet all of the following criteria: 1) residual neurologic symptoms \< grade 1, 2) no steroid requirement, 3) a follow-up MRI shows regression or stability of lesions after treatment, with no new lesions appearing
• Unable to swallow whole pills
• A requirement for one of the prohibited medications; if patient is currently taking one of these medications, they may be eligible so long as they discontinue the prohibited medication prior to starting study treatment and remain off for the duration they are taking study treatment

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fox Chase Cancer Center

Rockledge, Pennsylvania, 19046, United States

Location

Related Publications (1)

• Zibelman M, Wong YN, Devarajan K, Malizzia L, Corrigan A, Olszanski AJ, Denlinger CS, Roethke SK, Tetzlaff CH, Plimack ER. Phase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat in advanced renal cell carcinoma and other solid tumors. Invest New Drugs. 2015 Oct;33(5):1040-7. doi: 10.1007/s10637-015-0261-3. Epub 2015 Jun 20.

  PMID: 26091915 RESULT

MeSH Terms

Conditions

Lymphoma

Interventions

ridaforolimus; Vorinostat; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Elizabeth Plimack
• Organization: Fox Chase Cancer Center

Elizabeth.Plimack@fccc.edu

215-728-3889

Study Officials

• Elizabeth Plimack

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 26, 2010
• Study Start: October 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: February 21, 2021
• Results First Posted: February 21, 2021

Record last verified: 2021-02

Locations

US (1)