Gastroesophageal Junction AdenocarcinomaPhase 1NCT02389751
Ganetespib in Combination With Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Stage II-III Esophageal Cancer
A Phase 1 study testing Carboplatin, Ganetespib and Paclitaxel in people with Gastroesophageal Junction Adenocarcinoma and Malignant Neoplasm of the Cervical Esophagus, run by M.D. Anderson Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastroesophageal Junction Adenocarcinoma, Malignant Neoplasm of the Cervical Esophagus, Malignant Neoplasm of the Thoracic Esophagus
- What is being tested?
- Carboplatin, Ganetespib and Paclitaxel
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2015to 16 Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: GUARDIAN-1 Trial: A Phase 1 Study of Ganetespib in Combination With Chemoradiation for Stage II-III Esophageal Carcinoma
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.
Read the 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.
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.
- Conditions
- 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
- Being tested
- Carboplatin, Ganetespib, Paclitaxel, Radiation Therapy
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
GanetespibDrug
Also called Hsp90 Inhibitor STA-9090, STA-9090
Given IV
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiate, Irradiated, irradiation
Undergo radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ganetespib, paclitaxel, carboplatin, radiation) | Experimental | 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 Receives: Drug: Carboplatin; Drug: Ganetespib; Drug: Paclitaxel; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: 70 days
Secondary outcomes (4)
Response rate based on FDG-PET/CT +/- CT imaging response assessment after completion of chemoradiation
Measured: At 6 weeks after completion of chemoradiation therapy
OS
Measured: Up to 5 years
PFS
Measured: Up to 5 years
pCR for patients who undergo surgical resection after neoadjuvant therapy
Measured: Up to 10 weeks after completion of chemoradiation therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2015 (estimated)
- Study start10 Apr 2015
- Primary completion16 Jul 2019
- Study completion16 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastroesophageal Junction AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Steven Lin, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02389751
- Sponsor's protocol ID
- 2013-0815
- Other IDs
- NCI-2015-00492, 2013-0815, P30CA016672
- Status last verified
- Jul 2019
- First submitted
- 10 Mar 2015
- Last updated
- 24 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GUARDIAN-1 Trial: A Phase 1 Study of Ganetespib in Combination With Chemoradiation for Stage II-III Esophageal Carcinoma
- ClinicalTrials.gov ID
- NCT02389751
- Acronym / sponsor ID
- 2013-0815
- Conditions
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Apr 2015 (actual)
- Primary completion
- 16 Jul 2019 (actual)
- Study completion
- 16 Jul 2019 (actual)
- First posted
- 17 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ganetespib, paclitaxel, carboplatin, radiation) | Experimental | Drug: Carboplatin, Drug: Ganetespib, Drug: Paclitaxel, Radiation: Radiation TherapyPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (16 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Treatment (ganetespib, paclitaxel, carboplatin, radiation) |
| GanetespibAlso: Hsp90 Inhibitor STA-9090, STA-9090Given IV | Drug | Treatment (ganetespib, paclitaxel, carboplatin, radiation) |
| PaclitaxelAlso: Anzatax, Asotax, Bristaxol, PraxelGiven IV | Drug | Treatment (ganetespib, paclitaxel, carboplatin, radiation) |
| Radiation TherapyAlso: Cancer Radiotherapy, Irradiate, Irradiated, irradiationUndergo radiation therapy | Radiation | Treatment (ganetespib, paclitaxel, carboplatin, radiation) |
Primary outcome
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%.
4 secondary outcomes
Response rate based on FDG-PET/CT +/- CT imaging response assessment after completion of chemoradiation
Time frame: At 6 weeks after completion of chemoradiation therapy
OS
Time frame: Up to 5 years
PFS
Time frame: Up to 5 years
pCR for patients who undergo surgical resection after neoadjuvant therapy
Time frame: Up to 10 weeks after completion of chemoradiation therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Lin principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carboplatin, Ganetespib and Paclitaxel in people with Gastroesophageal Junction Adenocarcinoma and Malignant Neoplasm of the Cervical Esophagus, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2019.