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

NCT02530437 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 2014-0966NCI-2015-01554
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 5 weeks

• 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.

  Up to 4 years and 10 months

Secondary Outcomes (3)

• Change in Biomarker Expression Levels of Primary and Secondary Resistance

  Baseline to the time of surgery

• Relapse-free Survival

  Up to 4 years and 10 months

• Overall Survival

  Up to 4 years and 10 months

Study Arms (2)

Step I (taladegib, paclitaxel, carboplatin, and radiation)

EXPERIMENTAL

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

Drug: Carboplatin; Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Drug: Taladegib

Step II (taladegib, paclitaxel, carboplatin, and radiation)

EXPERIMENTAL

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

Drug: Carboplatin; Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Drug: Taladegib

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Step I (taladegib, paclitaxel, carboplatin, and radiation); Step II (taladegib, paclitaxel, carboplatin, and radiation)

External Beam Radiation Therapy RADIATION

Undergo external beam radiation therapy

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam

Step I (taladegib, paclitaxel, carboplatin, and radiation); Step II (taladegib, paclitaxel, carboplatin, and radiation)

Laboratory Biomarker Analysis OTHER

Correlative studies

Step I (taladegib, paclitaxel, carboplatin, and radiation); Step II (taladegib, paclitaxel, carboplatin, and radiation)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Step I (taladegib, paclitaxel, carboplatin, and radiation); Step II (taladegib, paclitaxel, carboplatin, and radiation)

Taladegib DRUG

Given PO

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

Step I (taladegib, paclitaxel, carboplatin, and radiation); Step II (taladegib, paclitaxel, carboplatin, and radiation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

Carboplatin; Radiation; Paclitaxel; Taxes; LY2940680; benzamide

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Physical Phenomena; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Dr. Jaffer Ajani
• Organization: University of Texas MD Anderson Cancer Center

jajani@mdanderson.org

(713) 792-2828

Study Officials

• Jaffer A Ajani

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2015
• First Posted: August 21, 2015
• Study Start: March 7, 2017
• Primary Completion: January 7, 2022
• Study Completion: January 7, 2022
• Last Updated: July 10, 2023
• Results First Posted: July 10, 2023

Record last verified: 2023-07

Locations

US (1)