Ganetespib in Combination With Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Stage II-III Esophageal Cancer

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT02389751

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

51.2

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Junction Adenocarcinoma Malignant Neoplasm of the Cervical Esophagus Malignant Neoplasm of the Thoracic Esophagus Stage IIA Esophageal Cancer AJCC v7 Stage IIB Esophageal Cancer AJCC v7 Stage IIIA Esophageal Cancer AJCC v7 Stage IIIB Esophageal Cancer AJCC v7 Stage IIIC Esophageal Cancer AJCC v7	Drug: Carboplatin Drug: Ganetespib Drug: Paclitaxel Radiation: Radiation Therapy	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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:

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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

GUARDIAN-1 Trial: A Phase 1 Study of Ganetespib in Combination With Chemoradiation for Stage II-III Esophageal Carcinoma

Actual Study Start Date :

Apr 10, 2015

Actual Primary Completion Date :

Jul 16, 2019

Actual Study Completion Date :

Jul 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Carboplatin Given IV Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Ganetespib Given IV Other Names: Hsp90 Inhibitor STA-9090 STA-9090 Drug: Paclitaxel Given IV Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Radiation: Radiation Therapy Undergo radiation therapy Other Names: Cancer Radiotherapy Irradiate Irradiated irradiation Radiation Radiotherapeutics RADIOTHERAPY RT Therapy, Radiation

Arm

Intervention/Treatment

Experimental: 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

Drug: Carboplatin

Given IV

Other Names:

Blastocarb

Carboplat

Carboplatin Hexal

Carboplatino

Carbosin

Carbosol

Carbotec

CBDCA

Displata

Ercar

JM-8

Nealorin

Novoplatinum

Paraplatin

Paraplatin AQ

Paraplatine

Platinwas

Ribocarbo

Drug: Ganetespib

Given IV

Other Names:

Hsp90 Inhibitor STA-9090

STA-9090

Drug: Paclitaxel

Given IV

Other Names:

Anzatax

Asotax

Bristaxol

Praxel

Taxol

Taxol Konzentrat

Radiation: Radiation Therapy

Undergo radiation therapy

Other Names:

Cancer Radiotherapy

Irradiate

Irradiated

irradiation

Radiation

Radiotherapeutics

RADIOTHERAPY

Therapy, Radiation

Outcome Measures

Primary Outcome Measures

MTD and recommended phase II dose of ganetespib, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [70 days]
The MTD is defined as the dose for which the posterior mean probability of dose-limiting toxicity is closest to 30%.

Secondary Outcome Measures

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]
PFS [Up to 5 years]
pCR for patients who undergo surgical resection after neoadjuvant therapy [Up to 10 weeks after completion of chemoradiation therapy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Hemoglobin >= 9 g/dL
Platelets >= 100x10^9/L
Albumin >= 2.5 g/dL
Serum bilirubin =< 1.5x institutional upper limit of normal (ULN)
Total bilirubin =< 1.5 x institutional ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x 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) =< 1.5 x institutional ULN
Baseline screening corrected QT (QTc) < 470 ms is eligible

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
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, g) if baseline QTc > 470 ms, average of triplicate electrocardiogram (ECG) recordings is necessary; if average value of QTc is

470 ms, patient is ineligible for the study; h) serum potassium, magnesium, and calcium levels outside the laboratory's reference range

Known immediate or delayed hypersensitivity reaction to carboplatin, paclitaxel, polysorbate 80, or any other component of the formulation
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
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
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) 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)
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)