A Trial of All-trans Retinoic Acid (ATRA) in Advanced Adenoid Cystic Carcinoma

NCT03999684 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-224
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This research is studying how safe and effective all-trans retinoic acid (ATRA), is to treat advanced adenoid cystic carcinoma (ACC).

Conditions

Adenoid Cystic Carcinoma

Keywords

Adenoid Cystic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate

  CR 0, PR 0, SD 11, PD 5, UE 2 Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. SD=stable disease, PD=progression of disease, UE=unevaluable

  up to 8 months

Secondary Outcomes (4)

• Complete Response

  up to 8 months

• Partial Response

  up to 8 months

• Progression Free Survival

  up to 8 months

• Duration Of Therapeutic Response

  up to 8 months

Other Outcomes (1)

• Number of Participants With no/Low, Medium MYB Expression in ACC Tumors

  up to 8 months

Study Arms (1)

Tretinoin

EXPERIMENTAL

-Participants will receive Tretinoin orally divided over two daily doses for days 1 through 14 of a 28-day cycle

Drug: Tretinoin

Interventions

Tretinoin DRUG

ATRA control normal cell growth, cell differentiation (the normal process of making cell different from each other), and cell death during embryonic development and in certain tissues later in life. Retinoids effects on the cells are controlled by receptors on the nucleus of each cell (nuclear receptors)

Also known as: Tretin-X, ATRA

Tretinoin

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed adenoid cystic carcinoma with evidence of recurrent, metastatic or advanced, unresectable disease that is not amenable to curative surgery with or without radiotherapy.
• Participants must have at least one RECIST v1.1 measurable non-CNS based lesion, as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) equal to or greater than 1 cm with CT scans or MR imaging.
• Participants must be willing to undergo fresh tissue core needle biopsy prior to study registration and repeat tumor biopsy while on study for correlatives. Willingness to provide blood samples for research throughout the study is also required.
• Prior systemic therapy: At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (4 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE Version 5.0 grade ≤ 1 (or tolerable grade 2) or back to baseline (except for alopecia or neuropathy). Any number of prior therapies for recurrent/metastatic ACC are permitted.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A).
• Participants must have documentation of a new or progressive lesion on a radiologic imaging study performed within 12 months prior to study registration (progression of disease over any interval is allowed) and/or new or worsening disease-related symptoms within 12 months prior to study registration. This assessment is performed by the treating investigator. Evidence of progression by RECIST v1.1 criteria is not required.
• Participants must have normal organ and marrow function as defined below (within 14 days prior to study registration):
• leukocytes ≥ 3,000/mcL
• absolute neutrophil count ≥ 1,500/mcL
• hemoglobin ≥ 9 g/dL without transfusion within 7 days of treatment
• platelets ≥ 100,000/mcL
• total bilirubin ≤ 2x upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤ 2.5x institutional ULN or ≤ 5x ULN for those with liver metastases
• serum creatinine ≤ 1.5x ULN OR

You may not qualify if:

• Metastatic disease impinging on the spinal cord or threatening spinal cord compression. Patients that have had previous treatment of disease with impinging on the cord with either surgery or radiotherapy with clinical or radiographic evidence of response or stability are eligible.
• Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment), and have no evidence of new or enlarging brain metastases. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability, because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Concurrent administration of other cancer specific therapy or investigational agents during the course of this study is not allowed.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Subjects who are pregnant, or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because tretinoin has the potential for teratogenic or abortifacient effects. Breastfeeding should be discontinued if the mother is treated on this protocol. Women who could potentially become pregnant while undergoing treatment on this protocol must be willing to use 2 methods of contraception.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• The V Foundation: collaborator
• Adenoid Cystic Carcinoma Research Foundation: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Interventions

Tretinoin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Dr. Glenn Hanna
• Organization: Dana-Farber Cancer Institute

glenn_hanna@dfci.harvard.edu

6176323090

Study Officials

• Glenn J. Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: June 27, 2019
• Study Start: August 5, 2019
• Primary Completion: April 15, 2020
• Study Completion: April 15, 2020
• Last Updated: January 23, 2023
• Results First Posted: August 6, 2021

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)