Phase I Trial of Ganetespib, Capecitabine, and Radiation in Rectal Cancer
Overview
- Phase
- Phase 1
- Intervention
- capecitabine + ganetespib
- Conditions
- Rectal Cancer
- Sponsor
- Emory University
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Tumor response and disease progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST).
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to find out what effects, good and/or bad, the combination of the study drug, capecitabine, and radiation have on you and your cancer. Capecitabine, radiation, and the study drug kill cancer cells in different ways. Giving these treatments together may make your cancer shrink or slow down its growth more than it would if you got treated with capecitabine and radiation alone.
This is a Phase I drug study of ganetespib given together with capecitabine and radiation in patients with locally advanced rectal cancer. Ganetespib is an experimental drug; not approved by the Food and Drug Administration (FDA). The other two, capecitabine and radiation, are approved by FDA for use in rectal cancer.
In this study, the investigators will test different dosages of the "investigational" (experimental) drug, called ganetespib (the study drug). The study drug is "investigational" because it is not approved by the FDA for use. The study drug has been previously tested in humans. The study uses a well-established process of slowly increasing drug dosage to determine the highest dosage that can be given without causing serious side effects. In addition, the study will help researchers to determine what the side effects and drug interactions might be.
The study will also look at the drug's pharmacokinetics (PK). PK is how the study drug and capecitabine with radiation work in your body (for example how long the drugs last in your body.)
Detailed Description
Patients with rectal cancer who meet the eligibility criteria will be offered to enroll on the study. As part of the study patients will receive the standard of care capecitabine (825 mg/m² by mouth twice daily) and radiation. Patients will start on ganetespib (STA9090) at a set dose level. The treatment consists of two parts. In the first part patients will receive ganetespib at full dose twice a week through the vein for two weeks. At the end of two weeks, a biopsy of the tumor will be performed to evaluate the effect of the drug on the tumor. In the second phase, patients will receive capecitabine, radiation and ganetespib at a specified dose level for 5 to 6 weeks. After completion of this phase, patients will have surgery to remove the tumor. Each three patients will be treated at a specified dose level. Patients will be monitored at least once a week for side effects. If there are no side effects in three consecutive patients, then the investigators will treat the next three patients at a higher dose level.
Investigators
Bassel El-Rayes
Principal Investigator
Emory University
Eligibility Criteria
Inclusion Criteria
- •Must be at least 18 years of age
- •Stage II or III histologically-proven rectal adenocarcinoma. The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by proctoscopic examination.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- •Adequate hematologic function as defined by:
- •Absolute neutrophil count ≥ 1,500 cells/µL
- •Platelets ≥ 100,000/µL
- •Hemoglobin ≥ 9.0g/dL
- •Adequate hepatic function as defined by:
- •Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
Exclusion Criteria
- •History of previous radiation therapy to the abdomen or pelvis
- •History of previous chemotherapy for rectal cancer
- •Major surgery within 4 weeks prior to first dose of ganetespib
- •Poor venous access for study drug administration. The study drug must be administered via peripheral venous access or through vascular access devices (VADs) (such as ports and peripherally-inserted central catheters \[PICCS\] containing silicone catheters. Use of VADs with catheters made of any other material is not allowed.
- •History of severe allergic or hypersensitivity reactions to excipients (e.g., Polyethylene glycol \[PEG\] 300 and Polysorbate 80)
- •Baseline corrected QT interval (QTc) \> 450 msec or previous history of QT prolongation while taking other medications
- •Ventricular ejection fraction (Ef) ≤ 55% at baseline
- •Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)
- •Women who are pregnant or lactating
- •Uncontrolled intercurrent illness
Arms & Interventions
capecitabine + ganetespib .
Capecitabine oral medication. Ganetespib IV medication
Intervention: capecitabine + ganetespib
Outcomes
Primary Outcomes
Tumor response and disease progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST).
Time Frame: 8 weeks
Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria.