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Gastroesophageal Junction AdenocarcinomaPhase 1/2NCT02530437

Taladegib, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Localized Esophageal or Gastroesophageal Junction Cancer

A Phase 1/2 study testing Carboplatin, External Beam Radiation Therapy and Laboratory Biomarker Analysis in people with Gastroesophageal Junction Adenocarcinoma and Stage IB Esophageal Adenocarcinoma AJCC v7, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase IB/II trial studies the side effects of taladegib, paclitaxel, carboplatin, and external beam radiation therapy and to see how well they work in treating patients with esophageal or gastroesophageal junction cancer found only in the tissue or organ where it began, and has not spread to nearby lymph nodes or… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, External Beam Radiation Therapy and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
7 Mar 2017to 7 Jan 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction (EAC)
  • Localized EAC and its baseline clinical stage determined as: T2-T3N0 or T1-3N positive (+); imaging studies suspicious for metastases must be followed with a negative biopsy before a patient can enter the study
  • Patients with malignant celiac nodes are eligible if the primary lesion is in the mid-thoracic or distal thoracic esophagus or it is involving the gastroesophageal junction
  • Tumor must have labeling index of >= 5% of the nuclear Gli-1 (integral biomarker) performed in the MD Anderson Cancer Center Clinical Laboratory Improvement Amendment (CLIA) laboratory for patient to be eligible in this trial (if enough archival tissue is not available to determine labeling index, patient must agree to a biopsy to be eligible for the study)
  • Tumor may not extend > 4 cm below the gastroesophageal junction
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
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  • All patients must be willing to provide research tumor tissue for biomarker studies at baseline, from archival tumor tissue or through endoscopy if sufficient archival tissue is not available; all patients must also allow biomarker studies on the tissue obtained through surgery to remove the primary cancer
  • Phase II only: patients volunteering for the Phase II part of the protocol must be willing to undergo a research endoscopy for tissue collection on day 8 (+/- 2 days) from the beginning of therapy
  • Absolute neutrophil count >= 1500/mm^3
  • Platelets greater >= 100,000/mm^3
  • Hemoglobin >= 8 g/dL
  • Serum creatinine =< 2 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
  • Serum bilirubin =< 1.5 x ULN
  • Patient must be able to comprehend the approved consent document and have the willingness to sign it; the patient prior to enrollment and the administration of any protocol-specific therapy must sign the consent document
  • Willingness and ability to comply with study procedures and follow-up examinations
  • Must be considered medically fit for operation as determined by multidisciplinary evaluation
  • Males and females with reproductive potential must agree to use 2 forms of medically approved contraceptive precautions and for at least 6 months following the last dose of biochemoradiation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Women of childbearing potential are defined as follows: having regular menstrual cycles; has amenorrhea, irregular menstrual cycles or using a contraceptive method that precludes withdrawal bleeding; have had a tubal ligation; women are considered not to be of childbearing potential for the following reasons: had hysterectomy and/or bilateral oophorectomy; post-menopausal defined by amenorrhea for at least 1 year in a woman > 45 years old
  • Females with childbearing potential must have a negative serum pregnancy test within 14 days prior to treatment start

Who cannot join

  • Baseline clinical stage of T1N0 or inoperable T4 (unequivocal organ involvement) are to be excluded
  • Unequivocal metastatic tumor at baseline
  • Tracheo-esophageal (TE) fistula or direct invasion into the tracheo-bronchial mucosa; a bronchoscopy (biopsy and cytology should be performed) is required to exclude TE fistula or tracheo-bronchial involvement in patients with a tumor located at < 26 cm from the incisors
  • Cervical esophageal cancer will not be entered in this study
  • Any prior chemotherapy, surgery, or radiotherapy for EAC
  • Prior mediastinal irradiation (for any reason)
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  • Clinically significant ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction are to be excluded
  • Malabsorption syndrome or other condition that would interfere with intestinal absorption are excluded
  • Pregnant or nursing females are to be excluded; breastfeeding should be discontinued if the mother is treated with taladegib
  • Presence of other significant cancer(s) or history of other significant cancer(s) within the last 3 years (patients who have been cancer-free for 3 years, or have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma of the cervix are eligible)
  • Known active viral or other chronic types hepatitides (hepatitis B, C) or cirrhosis
  • Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia that interfere with blood pressure, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with the study requirements
  • Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation
  • Patients who are receiving concurrent non-protocol anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or tumor embolization) are to be excluded
  • Patients may not be receiving any other investigational agents
  • Patients with known hypersensitivity to taxanes or platinums are to be excluded
  • Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin) are ineligible; patients on strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors will also be excluded
  • Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
  • Any other conditions or circumstances that would, in the opinion of the investigator, make the patient unsuitable for participation in the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 1B/2 Study of Taladegib in Combination With Weekly Paclitaxel, Carboplatin, and Radiation in Localized Adenocarcinoma of the Esophagus or Gastroesophageal Junction

This phase IB/II trial studies the side effects of taladegib, paclitaxel, carboplatin, and external beam radiation therapy and to see how well they work in treating patients with esophageal or gastroesophageal junction cancer found only in the tissue or organ where it began, and has not spread to nearby lymph nodes or to other parts of the body (localized). Taladegib 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 taladegib, paclitaxel, carboplatin, and radiation therapy may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the toxicity of taladegib administered orally daily concurrently with weekly paclitaxel, carboplatin and radiation therapy in patients with localized nuclear glioma-associated oncogene homolog (Gli-1) expressing adenocarcinoma of the esophagus or gastroesophageal junction. (Phase IB) II. To assess the rate of pathologic complete response (pathCR) when taladegib is administered orally daily concurrently with weekly paclitaxel, carboplatin, and radiation therapy in patients with localized nuclear Gli-1 expressing adenocarcinoma of the esophagus or gastroesophageal junction. (Phase II)

SECONDARY OBJECTIVES:

  1. To evaluate the toxicity of biochemoradiation in the phase II study. II. To assess additional biomarkers (hedgehog [Hh] related and Hh unrelated) in sequentially procured tissues (biopsies and resected specimens).

III. Assess if taladegib down modulates its target (Gli-1) in the first cohort (where taladegib will be administered alone for the first 7 days) of the phase II study.

IV. Assess relapse-free survival and overall survival.

OUTLINE:

PHASE IB: Patients receive taladegib orally (PO) once daily (QD) on days 1-38, paclitaxel intravenously (IV) over 3 hours on the first radiation day of each week for 5 doses, carboplatin IV over 2 hours on the first radiation day of each week for 5 doses, and undergo external beam radiation therapy 5 days weekly on 28 consecutive weekdays for 5.5 weeks.

PHASE II: Patients are assigned to 1 of 2 steps.

STEP I: Patients receive taladegib PO for 7 days, followed by taladegib, paclitaxel, carboplatin, and external beam radiation therapy as in Phase IB.

STEP II: Patients receive taladegib, paclitaxel, carboplatin, and external beam radiation therapy as in Phase IB.

After completion of study treatment, patients are followed up at 3 months, every 3-6 months for 1 year, every 6 months for 2 years, and at years 4 and 5.

Being tested
Carboplatin, External Beam Radiation Therapy, Laboratory Biomarker Analysis, Paclitaxel, Taladegib
Medical subject headings
Adenocarcinoma Of Esophagus

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

  • External Beam Radiation TherapyRadiation

    Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy

    Undergo external beam radiation therapy

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • TaladegibDrug

    Also called Benzamide, 4-Fluoro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)-1-phthalazinyl)-4-piperidinyl)-2-(trifluoromethyl)-, LY-2940680, LY2940680

    Given PO

Study groups in NCT02530437
Study groupRoleWhat they receive
Step I (taladegib, paclitaxel, carboplatin, and radiation)ExperimentalPatients receive taladegib PO for 7 days, followed by taladegib, paclitaxel, carboplatin, and external beam radiation therapy as in Phase IB.
Receives: Drug: Carboplatin; Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Drug: Taladegib
Step II (taladegib, paclitaxel, carboplatin, and radiation)ExperimentalPatients receive taladegib, paclitaxel, carboplatin, and external beam radiation therapy as in Phase IB.
Receives: Drug: Carboplatin; Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Drug: Taladegib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of Taladegib When Given in Combination With Paclitaxel, Carboplatin, and Radiation Therapy Defined by Dose-limiting Toxicities (Phase IB)

    The safety data will be summarized using frequencies and percentages by adverse event category, grade and attributions.

    Measured: Up to 5 weeks

  2. Pathologic Complete Response Rate (Phase II)

    A pathologic complete response (pathCR) rate of at least 35% (>= 40% is desirable) will be of interest. The pathCR rate in each of the treatment step will be estimated, along with the 95% confidence interval.

    Measured: Up to 4 years and 10 months

Secondary outcomes (3)

  1. Change in Biomarker Expression Levels of Primary and Secondary Resistance

    A linear mixed effect model will be used to assess the change of biomarkers over time. The outcome variable will be biomarker expression level and the covariates will include time, treatment step and time by treatment interaction. The biomarker expression may be log-transformed prior to fit the model in order to satisfy the normality assumption. Also, a logistic regression model will be used for the binary outcome of pathCR, using treatment step, baseline biomarker and the change of biomarker between baseline and at surgery as covariates.

    Measured: Baseline to the time of surgery

  2. Relapse-free Survival

    Kaplan-Meier method will be used to estimate the probabilities of relapse-free survival.

    Measured: Up to 4 years and 10 months

  3. Overall Survival

    Kaplan-Meier method will be used to estimate the probabilities of overall survival.

    Measured: Up to 4 years and 10 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2015 (estimated)
  2. Study start7 Mar 2017
  3. Primary completion7 Jan 2022
  4. Study completion7 Jan 2022

Why it stopped: The sponsor sold the drug TALADEGIB to another company during the trial and thereafter no drug was available. The sponsor made a decision to stop development of this drug Taladegib.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02530437
Sponsor's protocol ID
2014-0966
Other IDs
NCI-2015-01554, 2014-0966
Status last verified
Jul 2023
First submitted
19 Aug 2015
Last updated
10 Jul 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carboplatin, External Beam Radiation Therapy and Laboratory Biomarker Analysis in people with Gastroesophageal Junction Adenocarcinoma and Stage IB Esophageal Adenocarcinoma AJCC v7, 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 20 inclusion and 19 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: stopped early, as of the sponsor's last update on 10 Jul 2023. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Safety of Taladegib When Given in Combination With Paclitaxel, Carboplatin, and Radiation Therapy Defined by Dose-limiting Toxicities (Phase IB) (time frame: Up to 5 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02530437.

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 10 Jul 2023.

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