Phase IIB Randomized, Placebo-Controlled Trial of ACTOplus Met® XR in Subjects With Stage I-IV Squamous Cell Carcinoma of the Oral Cavity or Oropharynx Prior to Definitive Treatment

Status: Terminated
Location: See all (4) locations...
Intervention Type: Other, Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This randomized phase IIb trial studies how well ACTOplus met XR works in treating in patients with stage I-IV oral cavity or oropharynx cancer that are undergoing definitive treatment. Chemoprevention is the use of drugs to keep oral cavity or oropharynx cancer from forming or coming back. The use of ACTOplus met XR may slow disease progression in patients with oral cavity or oropharynx cancer.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• Participant has a newly diagnosed, histologically confirmed, stage I-IV squamous cell carcinoma or squamous cell carcinoma in situ of the oral cavity or oropharynx and will be undergoing definitive surgical, radiotherapy, or chemoradiation treatment; patients who are NOT candidates for localized treatment (surgery, radiation or chemoradiation) with curative intent (i.e.patients with distant metastasis or contra-indication to localized treatment) are not eligible OR

• Participant has a lesion in the oral cavity or oropharynx that is not yet biopsied but is highly suspicious for cancer; (randomization will be placed on hold until the presence of cancer is histologically confirmed, and a treatment plan is established; if the presence of cancer is not confirmed, the participant will be considered a screen failure)

• The participant's primary tumor is accessible for the collection of 4 mm samples of tumor and adjacent visually normal appearing tissue for biomarker analysis and the participant is willing to have these samples collected at baseline and at the end of study visit. (The protocol requires the collection of fresh tissue for biomarker analysis)

• Patients who have not yet had a diagnostic biopsy:

• The tissue samples for biomarker analysis may be collected in conjunction with the patient's standard of care diagnostic biopsy but not until after the patient has signed informed consent and it has been determined that they meet all of the eligibility criteria for this protocol with the exception of normal organ and marrow function as defined by the clinical laboratory test results listed for that criterion. In this situation, because the patient would be having a biopsy regardless of whether or not they were participating in this study, it is not required to obtain these results prior to conducting the biopsy. It is however, required to confirm normal organ and marrow function prior to randomization.

• Patients who are scheduled for a direct operative laryngoscopy with biopsy (DL biopsy) for diagnostic purposes may be candidates for this study provided the following criteria are met:

• The lesion to be biopsied is within the anatomic confines of the oropharynx (i.e. above the epiglottis).

• Tissue samples for biomarker analysis of the required 4 mm size are able to be obtained from both the lesion and an area of visually normal appearing tissue adjacent to but 1 cm distant from the lesion.

• In this situation, randomization will be placed on hold until the following criteria are met:

• Normal organ and marrow function is confirmed.

• There is histologic confirmation of squamous cell carcinoma.

• It has been determined that surgical excision will be the first line standard of care treatment and the end of study tissue samples will be obtained in conjunction with that surgery.

• Because these patient's lesions are not accessible to end of study tissue sample collection in the outpatient clinic setting, the only way to obtain those samples is in conjunction with standard of care surgical excision of the lesion. If the first line of treatment will be non-surgical, the patient will be considered a screen failure. Under no circumstances will DL biopsy be used for the sole purpose of collecting tissue samples for biomarker analysis.

• Patients who have already had a diagnostic biopsy:

• The baseline tissue samples for biomarker analysis will be collected in the outpatient clinic setting as a for research purposes only procedure. The samples may not be collected until it has been determined that the participant meets all eligibility criteria for this protocol.

• End of study tissue sample collection:

• If surgical excision will be the patient's first line treatment, the end of study tissue samples for biomarker analysis will be collected in conjunction with that surgery. If, for any reason, the patient's surgery is delayed beyond Day 26, the end of study tissue samples may be collected in the outpatient clinic setting.

• If the patient's first line of treatment will not be surgical excision, the end of study tissue samples for biomarker analysis will be collected in the outpatient clinic setting prior to initiation of the non-surgical treatment.

• Participant is able to complete a minimum of 10 days of study agent dosing prior to initiation of definitive treatment for their cancer

• Participant is scheduled for an end of study biopsy within 22 days of starting study agent and within 52 days of their study screening visit; (if the participant is scheduled for surgical excision of the tumor and the surgery is delayed for any reason after the participant has started taking the study agent, study agent dosing may be extended up to a maximum of 25 days without compromising the evaluability of the end of study biomarkers)

• Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1

• Life expectancy is > 6 months

• Body mass index (BMI) is >= 18.5

• Hemoglobin >= 10 g/dl

• White blood cells >= 3,000/microliter

• Platelets >= 100,000/microliter

• Total bilirubin =< 1.2 x institutional upper limit of normal

• With the exception of candidates with a diagnosis of Gilbert's disease in which case the total bilirubin may extend up to 1.5 x institutional upper limit of normal

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 1.2 x institutional upper limit of normal

• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.2 x institutional upper limit of normal

• Glucose, serum < 200 mg/dL

• Estimated glomerular filtration rate (eGFR) > 45 mL/min (if eGFR is not included on the clinical lab report, the chronic kidney disease epidemiology [CKD-EPI] creatinine calculator may be used)

• Participant is able to swallow a tablet whole

• Participant is willing and able to participate for the duration of the study

• Participant of childbearing potential agrees to use adequate contraception (a hormonal method that has been in continual use for a minimum of 3 months prior to the study screening visit, a barrier method, or abstinence) for the duration of their study participation. (Therapy with pioglitazone may result in ovulation in some premenopausal anovulatory women. In addition, the effects of ACTOplus Met XR on the developing human fetus at the recommended therapeutic dose are unknown. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.)

• Note: Due to the risks associated with hormonal methods of birth control, participants should not start hormonal therapy for the purpose of meeting the eligibility criteria for this protocol.

• Ability to understand and the willingness to sign a written informed consent document

Locations
United States
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore
Minnesota
University of Minnesota/Masonic Cancer Center
Minneapolis
New York
University of Rochester
Rochester
Wisconsin
University of Wisconsin Hospital and Clinics
Madison
Time Frame
Start Date: August 14, 2017
Completion Date: August 28, 2019
Participants
Target number of participants: 13
Treatments
Experimental: Group I (ACTOplus met XR)
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Placebo Comparator: Group II (placebo)
Patients receive placebo PO QD daily for 10-21 days.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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