Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02389751
Other study ID # 2013-0815
Secondary ID NCI-2015-0049220
Status Completed
Phase Phase 1
First received
Last updated
Start date April 10, 2015
Est. completion date July 16, 2019

Study information

Verified date July 2019
Source M.D. Anderson Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 3
Est. completion date July 16, 2019
Est. primary completion date July 16, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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)

Study Design


Related Conditions & MeSH terms

  • Adenocarcinoma
  • Esophageal Neoplasms
  • Gastroesophageal Junction Adenocarcinoma
  • Malignant Neoplasm of the Cervical Esophagus
  • Malignant Neoplasm of the Thoracic Esophagus
  • Neoplasms
  • 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

Intervention

Drug:
Carboplatin
Given IV
Ganetespib
Given IV
Paclitaxel
Given IV
Radiation:
Radiation Therapy
Undergo radiation therapy

Locations

Country Name City State
United States M D Anderson Cancer Center Houston Texas

Sponsors (2)

Lead Sponsor Collaborator
M.D. Anderson Cancer Center National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary MTD and recommended phase II dose of ganetespib, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 The MTD is defined as the dose for which the posterior mean probability of dose-limiting toxicity is closest to 30%. 70 days
Secondary Response rate based on FDG-PET/CT +/- CT imaging response assessment after completion of chemoradiation At 6 weeks after completion of chemoradiation therapy
Secondary OS Up to 5 years
Secondary PFS Up to 5 years
Secondary pCR for patients who undergo surgical resection after neoadjuvant therapy Up to 10 weeks after completion of chemoradiation therapy
See also
  Status Clinical Trial Phase
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Completed NCT02128243 - Trial of S-1 Maintenance Therapy in Metastatic Esophagogastric Cancer Phase 2
Active, not recruiting NCT05008783 - A Study of AK104 in the First-line Treatment of Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma Phase 3
Recruiting NCT04140526 - Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC Phase 1/Phase 2
Recruiting NCT03421288 - Study of Atezolizumab + FLOT vs. FLOT Alone in Patients With GC/GEJ and High Immune Responsiveness Phase 2
Completed NCT03196232 - Epacadostat and Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Junction or Gastric Cancer Phase 2
Terminated NCT03511222 - Vorolanib (X-82) Combined With Checkpoint Inhibitors in Patients With Solid Tumors Phase 1
Completed NCT02891447 - Heated Mitomycin and Cisplatin During Surgery in Treating Patients With Stomach or Gastroesophageal Cancer Phase 2
Completed NCT02864381 - Study to Evaluate the Efficacy and Safety of Andecaliximab Combined With Nivolumab Versus Nivolumab Alone in Adults With Unresectable or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Phase 2
Terminated NCT04032704 - A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors Phase 2
Active, not recruiting NCT03615326 - Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811) Phase 3
Completed NCT02830594 - Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer Phase 2
Completed NCT02539225 - A Study of Ramucirumab in Participants With Gastric or Gastroesophageal Junction Adenocarcinoma Phase 2
Recruiting NCT06038578 - A Study of TRK-950 When Used in Combination With Ramucirumab and Paclitaxel in Patients With Gastric Cancer Phase 2
Completed NCT04808791 - iTTo for Treatment Naive Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma Phase 2
Recruiting NCT04581473 - Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CT041 Autologous CAR T-cell Injection Phase 1/Phase 2
Completed NCT00515411 - Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) in Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma Phase 2
Recruiting NCT06206278 - Evaluation of Infigratinib in Patients With Locally Advanced or Metastatic Gastric Cancer or GEJ Adenocarcinoma Phase 2
Recruiting NCT05902988 - A Phase I/II Study of VLS-1488 in Subjects With Advanced Cancer Phase 1/Phase 2