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

Gastroesophageal Junction Adenocarcinoma Clinical Trial

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

Status Terminated

Clinical 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 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.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. 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:

I. 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. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Neoplasms
• Gastroesophageal Junction Adenocarcinoma
• Stage IB Esophageal Adenocarcinoma AJCC v7
• Stage II Esophageal Adenocarcinoma AJCC v7
• Stage IIA Esophageal Adenocarcinoma AJCC v7
• Stage IIB Esophageal Adenocarcinoma AJCC v7
• Stage IIIA Esophageal Adenocarcinoma AJCC v7
• Stage IIIB Esophageal Adenocarcinoma AJCC v7

• NCT number: NCT02530437
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 7, 2017
• Completion date: January 7, 2022