Ganetespib in Combination with Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients with Stage II-III Esophageal Cancer
This trial is active, not recruiting.
|Treatments||ganetespib, carboplatin, paclitaxel, radiotherapy|
|Targets||Hsp90, BCR-ABL, EGFR, KIT|
|Sponsor||M.D. Anderson Cancer Center|
|Collaborator||Synta Pharmaceuticals Corp.|
|Start date||April 2015|
|End date||April 2018|
|Trial size||40 participants|
|Trial identifier||NCT02389751, 2013-0815, NCI-2015-00492|
The goal of this clinical research study is to find the highest tolerable dose of ganetespib that can be given in combination with standard chemotherapy (paclitaxel and carboplatin) and radiation therapy in patients with esophageal cancer.
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Maximum Tolerated Dose (MTD) and Recommended Phase II Dose of Ganetespib to Combine with Standard Carboplatin and Paclitaxel Chemotherapy and Radiotherapy
time frame: 70 days
Response Rate based on FDG-PET/CT +/- CT
time frame: 12 weeks
Male or female participants at least 18 years old.
Inclusion Criteria: 1. Histologically documented adenocarcinoma or squamous cell carcinoma of the cervical esophagus, thoracic esophagus, or gastroesophageal junction 2. Stage II or III esophageal carcinoma according to the AJCC 7th edition staging 3. EGD with EUS +/- biopsy at M.D. Anderson are required to confirm staging 4. ECOG performance status = 1 (Karnofsky >/= 70%) 5. Patients should have no contraindications for chemotherapy or radiation, and should receive either definitive chemoradiation therapy or preoperative chemoradiation therapy 6. Age >/= 18 years, as there are currently no dosing or adverse event data available on the use of Ganetespib in patients < 18 years of age 7. Patients must have received baseline FDG-PET/CT +/- CT with contrast within 1 month +/- 2 weeks prior to study entry, and should have no contraindications to PET or CT imaging 8. There are no adequate and well-controlled studies in pregnant women using Ganetespib. For this reason and because radiation is known to be teratogenic, both women of child-bearing potential and men must agree to adequate contraception (hormonal or barrier method of birth control; abstinence) during and up to 30 days after discontinuing treatment 9. Women of child-bearing potential must have a negative serum pregnancy test within 14 days of study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately 10. Patients must have adequate organ and marrow function as defined: *Absolute neutrophil count (ANC) >/= 1.5x109/L; *WBC >/= 2500 cells/µl; *Hemoglobin >/= 9 g/dL; *Platelets >/= 100x109/L; *Albumin >/= 2.5 g/dL; *Serum bilirubin = 1.5x institutional upper limit of normal (ULN); *Total bilirubin = 1.5x institutional ULN; *Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5x institutional ULN; *Serum creatinine = 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >/= 50 mL/min OR 24-hour urine creatinine clearance >/= 50 mL/min; *Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) = 1.5x institutional ULN 11. Baseline screening QTc < 470 ms is eligible. Exclusion Criteria: 1. Prior radiation to the chest or abdomen 2. Previous or concomitant malignancy - EXCEPTIONS: Patients with curatively treated carcinoma in situ of the cervix, basal cell of the skin, transitional cell carcinoma of the bladder, or early stage cancers at non-overlapping sites with no evidence of disease for >/= 3 years. 3. No induction chemotherapy 4. Pregnant or breast-feeding females. Patients who become pregnant during active therapy will be immediately removed from the study. 5. Uncontrolled intercurrent illness or serious medical conditions including, but not limited to: *Clinically significant, uncontrolled, major cardiac, respiratory, renal, hepatic, gastrointestinal, or hematologic disease; *Active uncontrolled infection; *Symptomatic congestive heart failure, unstable angina, or cardiac dysrrhythmia not controlled by pacer device; *No myocardial infarction within 3 months of registration; *Symptomatic inflammatory bowel disease with uncontrolled diarrhea 6. Major cardiac-related diseases, medications, or laboratory abnormalities including the following: a) Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker, b) Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic drug (eg, sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted. c) Use of medications that have been linked to the occurrence of torsades de pointes, d) Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker, e) Complete left bundle branch block (LBBB), f) History of long QT Syndrome or a family member with this condition, 7. Exclusion #6 continued: g) If baseline QTc >470 ms, average of triplicate ECG recordings is necessary. If average value of QTc is >470ms, patient is ineligible for the study. h) Serum potassium, magnesium, and calcium levels outside the laboratory's reference range. 8. Known immediate or delayed hypersensitivity reaction to carboplatin, paclitaxel, polysorbate 80, or any other component of the formulation 9. Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to study registration, and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to registration 10. Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) either preceding the first dose of Ganetespib or during the study period 11. Current use of a prohibited medication. The following medications or non-drug therapies are prohibited: a) Other anti-cancer therapy while on study treatment, b) Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], gingko biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng) 12. Known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), or active Hepatitis C virus (HCV) infection (with the exception of chronic or cleared HBC and HCV infection, which will be allowed).
|Official title||GUARDIAN-1 Trial: A Phase 1 Study of Ganetespib in Combination With Chemoradiation for Stage II-III Esophageal Carcinoma|
|Principal investigator||Steven H. Lin, MD, PHD|
|Description||Study Groups: If participant is found to be eligible to take part in this study, they will be assigned to a dose level of ganetespib based on when they joined this study. Up to 3 dose levels of ganetespib will be tested. The first group of participants will receive the lowest dose level. Each new group will then receive a higher dose level than the group before it, if no intolerable side effects are seen. This will continue until the highest tolerable dose of ganetespib is found. All participants will receive the same standard dose level of paclitaxel and carboplatin. Study Treatment: Participant will also receive radiation therapy for 5 days a week (Monday-Friday) for about 5 ½ weeks. Each radiation treatment will take only a few minutes, but the appointment will last about 1 hour. On the first day of radiation (Monday, Tuesday, or Wednesday) and then every week after that during radiation, participant will receive ganetespib. Participant will also be given paclitaxel by vein over about 1 hour and carboplatin by vein over about 30 minutes. Study Tests: Each week during treatment for Weeks 1, 2, and 3: - Participant will have a physical exam. - Blood (up to 2 teaspoons) will be drawn for routine tests. - Participant will have an EKG right before the ganetespib infusion and then 24hours after the ganetespib infusion. Each week during treatment for Weeks 4 and 5: - Participant will have a physical exam. - Blood (up to 2 teaspoons) will be drawn for routine tests. - Participant will have an EKG right before the ganetespib infusion. Participant will have another EKG 24 hours after the infusion if they have a previous abnormal EKG result. Participant's dose of ganetespib may be adjusted or stopped at any time based on their EKG results. About 6 weeks after treatment, participant will have the following tests and procedures to help their doctor decide if they should have standard of care surgery: - Participant will have a physical exam. - Blood (up to 2 teaspoons) will be drawn for routine tests. - Participant will have an FDG-PET/CT scan and/or CT scan to check the status of the disease. - Participant will have an endoscopic biopsy to check the status of the disease. Surgery: If participant's doctor decides they should have surgery, the surgery will be performed at MD Anderson about 8 to 10 weeks after finishing chemotherapy and radiation therapy. If participant needs surgery, they will be given a separate consent form that describes the surgery and its risks. At the time of surgery, participant will have a physical exam as part of routine care. Length of Treatment: Participant will receive the treatment for up to 6 weeks. Participant will no longer be able to receive treatment if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions. Patient's participation on the study will be over after the follow-up visits. Follow-up Testing: If the disease comes back while participant is on study, the following tests will be performed: - Participant will have a physical exam. - Participant will have an endoscopic biopsy to check the status of the disease. - If not already done, participant will have a CT scan or an FDG-PET/CT scan to check the status of the disease. Participant will be asked to return to the clinic for follow-up tests. Participants will have follow-up visits every 3 months for up to 1 year, unless they are taken off study. After 1 year, participant will have follow-up visits about every 4 months in the second year after radiation therapy, and then about every 6 months for the next 3 years. At these follow-up visits, the following tests will be performed: - Participant will have a physical exam. - Blood (up to 2 teaspoons) will be drawn for routine tests. - Participant will have a PET/CT and/or CT scan to check the status of the disease. - If participant's doctor thinks it is in their best interest, they will have an endoscopic biopsy to check the status of the disease. - Participant will also receive nutritional assessment and counseling, if needed. This is an investigational study. Ganetespib is not FDA approved or commercially available. It is currently being used for research purposes only. Paclitaxel, carboplatin, and radiation therapy are all FDA approved and considered standard treatment for esophageal cancer. The combination of paclitaxel, carboplatin, ganetespib, and radiation therapy is investigational. The study doctor can explain how the study drugs are designed to work. Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.|
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