Study of RAD001 in Adenoid Cystic Carcinoma (ACCRAD001)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by Seoul National University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01152840
First received: May 31, 2010
Last updated: June 28, 2010
Last verified: June 2010
  Purpose
  • Although mTOR is clearly an attractive therapeutic target in tumor, no clinical study on mTOR inhibition by RAD001 has been systematically conducted in adenoid cystic carcinoma.
  • In phase I study of RAD001, 2 patients with adenoid cystic carcinoma show some response to RAD001 (unpublished data).
  • So the investigators design this phase II study of RAD001 in adenoid cystic carcinoma to evaluate the efficacy of RAD001 in this orphan disease.

Condition Intervention Phase
Adenoid Cystic Carcinoma
Drug: RAD001
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of RAD001monotherapy in Patients With Unresectable Adenoid Cystic Carcinoma

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • progression free survival rate at 4 months [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    proportion of patients who are alive and progression-free at the time of 4 months of treatment among all patients


Secondary Outcome Measures:
  • the time to progression (TTP) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  • overall survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • response rate (RR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • the metabolic response rate by PET-CT [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: July 2008
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001
RAD001 daily po medication
Drug: RAD001

RAD001 10 mg po daily medication

  • Treatments will be continued until any of the following events occur:

    • progression of disease,
    • the subject develops unacceptable toxicity,
    • consent to participate in the study is withdrawn.

Detailed Description:

Although the histologic appearance of adenoid cystic carcinoma is low grade, management of this malignancy is a distinct therapeutic challenge because of its insidious local growth pattern, propensity for perineural involvement, tendency for distant metastasis, and pronounced ability to recur over a prolonged period.

In prospectively performed clinical trials, objective responses to any cytotoxic agent or regimen are infrequent, whereas stabilization of disease was observed more commonly.

In adenoid cystic carcinoma, the study focusing on PI3-K/AKT/mTOR pathway is rare.

According to Younes MN et al's study, adenoid cystic carcinoma cell lines have increased pAkt activity when EGF-stimulation is added. And when treated with EGFR/VEGFR TK dual inhibitor, the phosphorylated form of Akt decreased despite of total level of Akt is remained unchanged.

When the investigators consider that the increased pAkt activity is one of possible predictor to mTOR inhibitor, the mTOR inhibitor might have an activity in adenoid cystic carcinoma.

Although mTOR is clearly an attractive therapeutic target in tumor, no clinical study on mTOR inhibition by RAD001 has been systematically conducted in adenoid cystic carcinoma.

In phase I study of RAD001, 2 patients with adenoid cystic carcinoma show some response to RAD001 (unpublished data).

So the investigators design this phase II study of RAD001 in adenoid cystic carcinoma to evaluate the efficacy of RAD001 in this orphan disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Histologically or cytologically confirmed adenoid cystic carcinoma
  • 2. Local, locally-advanced or metastatic disease documented as having shown progression on a scan (CT, MRI, MIBI scan) taken 2 to 12 months prior to baseline compared to a previous scan taken at any time in the past. Progression must be documented according to RECIST criteria.
  • 3. Disease that is not amenable to surgery, radiation or combined modality therapy with curative intent and who is previously treated with chemotherapy or local treatment (e,g transarterial chemoembolization)
  • 4. Presence of at least one measurable target lesion for further evaluation according to RECIST criteria
  • 5. 18 years or older
  • 6. ECOG performance status 0, 1
  • 7. Previous treatment with chemotherapy, loco-regional therapy (e.g chemoembolization) are permitted providing that toxicity has resolved to ≤grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment.
  • 8. Adequate organ function
  • 9. A patient with the willingness to comply with the study protocol during the study period and capable of complying with it
  • 10. A patient who signed the informed consent prior to the participation of the study and who understands that he/she has a right to withdrawal from participation in the study at any time without any disadvantages.

Exclusion Criteria:

  • 1. A patient with no measurable disease
  • 2. Prior chemotherapy, radiation therapy or surgery within 4 weeks prior to study entry except palliative radiotherapy to non-target lesions (within 2 weeks prior to study entry)
  • 3. A patient with previous active or passive immunotherapy
  • 4. A patient with intestinal obstruction or impending obstruction, recent active upper GI bleeding
  • 5. A pregnant or lactating patient
  • 6. A patient of childbearing potential without being tested for pregnancy at baseline or with being tested for positive. (A postmenopausal woman with the amenorrhea period of at least 12 months or longer is considered to have non-childbearing potential)
  • 7. A man or woman of childbearing potential who has no willingness to use a contraceptive measure during the study
  • 8. A patient with history of another malignant disease within past 5 years, except curatively treated basal cell carcinoma of skin and cervical carcinoma in situ.
  • 9. A patient with history of uncontrolled seizures, central nervous system disorder or psychiatric disorders that are considered clinically significant by the investigator that would prohibit the understanding of informed consent or that may be considered to interfere with the compliance of the administration of the study medications.
  • 10. A patient with clinically significant heart disease (e.g. congestive heart failure, symptomatic coronary artery diseases, cardiac arrhythmia, etc) or myocardial infarction within past 12 months.
  • 11. Ongoing cardiac arrhythmia of grade ≥2, atrial fibrillation of any grade, or QTc interval>450msec for males or >470msec for female.
  • 12. A patient with interstitial pneumonia or diffuse symptomatic fibrosis of the lungs
  • 13. A patient with peripheral neuropathy of grade 1 by NCI CTC, caused by other factors (e.g. alcohol, diabetes, etc). If the absence of deep tendon reflexes is the only neurologic disorder, this condition does not apply to the exclusion criteria.
  • 14. A patient with organ transplantation requiring immunosuppressive therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01152840

Contacts
Contact: Yung-Jue Bang, MD,PhD 82-2-2072-2390 bangyj@snu.ac.kr
Contact: Do-Youn Oh, MD,PhD 82-2-2072-0701 ohdoyoun@snu.ac.kr

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Yung-Jue Bang, MD, PhD    82-2-2072-2390    bangyj@snu.ac.kr   
Contact: Do-Youn Oh, MD, PhD    82-2-2072-0701    ohdoyoun@snu.ac.kr   
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Yung-Jue Bang, MD, PhD Seoul National University Hospital
Study Director: Do-Youn Oh, MD,PhD Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Yung-Jue Bang/Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01152840     History of Changes
Other Study ID Numbers: H-0710-050-223
Study First Received: May 31, 2010
Last Updated: June 28, 2010
Health Authority: Korean Food and Drug Administration:Korea, Republic of

Keywords provided by Seoul National University Hospital:
Adenoid cystic carcinoma
RAD001

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Adenoid Cystic
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 22, 2014