GUARDIAN-1 Trial: A Phase 1 Study of Ganetespib in Combination With Chemoradiation for Stage II-III Esophageal Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Carboplatin
- Conditions
- Gastroesophageal Junction Adenocarcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- MTD and recommended phase II dose of ganetespib, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This phase I trial studies the side effects and best dose of ganetespib when given together with paclitaxel, carboplatin, and radiation therapy in treating patients with stage II-III esophageal cancer. Ganetespib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving ganetespib in combination with paclitaxel, carboplatin, and radiation therapy may be a better treatment for patients with esophageal cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated disease (MTD) and the recommended phase II dose of ganetespib to combine with standard carboplatin and paclitaxel chemotherapy and radiotherapy in stage II-III patients with esophageal carcinoma. SECONDARY OBJECTIVES: I. To assess the response rate based on fludeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) +/- CT with contrast imaging response assessment after completion of chemoradiation. II. To determine the 1 year overall survival (OS) rate. III. To determine the progression-free survival (PFS) rate. IV. To determine the pathologic complete response (pCR) rate for patients who undergo surgery. OUTLINE: This is a dose-escalation study of ganetespib. Patients receive ganetespib intravenously (IV) over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes once a week on day 1. Patients also undergo radiation therapy 5 days a week for 5.5 weeks or for a total of 28 treatments. Treatment continues for 28 treatment days (5.5 weeks) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically documented adenocarcinoma or squamous cell carcinoma of the cervical esophagus, thoracic esophagus, or gastroesophageal junction
- •Stage II or III esophageal carcinoma according to the American Joint Committee on Cancer (AJCC) 7th edition staging
- •Esophagogastroduodenoscopy (EGD) with endoscopic ultrasound (EUS) +/- biopsy at M.D. Anderson are required to confirm staging
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
- •Patients should have no contraindications for chemotherapy or radiation, and should receive either definitive chemoradiation therapy or preoperative chemoradiation therapy
- •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
- •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
- •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
- •Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
- •White blood cells (WBC) \>= 2500 cells/ul
Exclusion Criteria
- •Prior radiation to the chest or abdomen
- •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
- •No induction chemotherapy
- •Pregnant or breast-feeding females; patients who become pregnant during active therapy will be immediately removed from the study
- •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 dysrhythmia not controlled by pacer device
- •No myocardial infarction within 3 months of registration
- •Symptomatic inflammatory bowel disease with uncontrolled diarrhea
Arms & Interventions
Treatment (ganetespib, paclitaxel, carboplatin, radiation)
Patients receive ganetespib IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes once a week on day 1. Patients also undergo radiation therapy 5 days a week for 5.5 weeks or for a total of 28 treatments. Treatment continues for 28 treatment days (5.5 weeks) in the absence of disease progression or unacceptable toxicity
Intervention: Carboplatin
Treatment (ganetespib, paclitaxel, carboplatin, radiation)
Patients receive ganetespib IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes once a week on day 1. Patients also undergo radiation therapy 5 days a week for 5.5 weeks or for a total of 28 treatments. Treatment continues for 28 treatment days (5.5 weeks) in the absence of disease progression or unacceptable toxicity
Intervention: Ganetespib
Treatment (ganetespib, paclitaxel, carboplatin, radiation)
Patients receive ganetespib IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes once a week on day 1. Patients also undergo radiation therapy 5 days a week for 5.5 weeks or for a total of 28 treatments. Treatment continues for 28 treatment days (5.5 weeks) in the absence of disease progression or unacceptable toxicity
Intervention: Paclitaxel
Treatment (ganetespib, paclitaxel, carboplatin, radiation)
Patients receive ganetespib IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes once a week on day 1. Patients also undergo radiation therapy 5 days a week for 5.5 weeks or for a total of 28 treatments. Treatment continues for 28 treatment days (5.5 weeks) in the absence of disease progression or unacceptable toxicity
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
MTD and recommended phase II dose of ganetespib, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame: 70 days
The MTD is defined as the dose for which the posterior mean probability of dose-limiting toxicity is closest to 30%.
Secondary Outcomes
- PFS(Up to 5 years)
- Response rate based on FDG-PET/CT +/- CT imaging response assessment after completion of chemoradiation(At 6 weeks after completion of chemoradiation therapy)
- OS(Up to 5 years)
- pCR for patients who undergo surgical resection after neoadjuvant therapy(Up to 10 weeks after completion of chemoradiation therapy)