Phase I Trial of Ganetespib, Capecitabine, and Radiation in Rectal Cancer

NCT01554969 | Completed Phase 1 DMC

• 2 other identifiers: IRB00054181STA 9090
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out what effects, good and/or bad, the combination of the study drug, capecitabine, and radiation have on you and your cancer. Capecitabine, radiation, and the study drug kill cancer cells in different ways. Giving these treatments together may make your cancer shrink or slow down its growth more than it would if you got treated with capecitabine and radiation alone. This is a Phase I drug study of ganetespib given together with capecitabine and radiation in patients with locally advanced rectal cancer. Ganetespib is an experimental drug; not approved by the Food and Drug Administration (FDA). The other two, capecitabine and radiation, are approved by FDA for use in rectal cancer. In this study, the investigators will test different dosages of the "investigational" (experimental) drug, called ganetespib (the study drug). The study drug is "investigational" because it is not approved by the FDA for use. The study drug has been previously tested in humans. The study uses a well-established process of slowly increasing drug dosage to determine the highest dosage that can be given without causing serious side effects. In addition, the study will help researchers to determine what the side effects and drug interactions might be. The study will also look at the drug's pharmacokinetics (PK). PK is how the study drug and capecitabine with radiation work in your body (for example how long the drugs last in your body.)

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Tumor response and disease progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST).

  Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria.

  8 weeks

Study Arms (1)

capecitabine + ganetespib .

EXPERIMENTAL

Capecitabine oral medication. Ganetespib IV medication

Drug: capecitabine + ganetespib

Interventions

capecitabine + ganetespib DRUG

Capecitabine will be started on Day 1 of the concurrent chemo-radiation phase at the specified dose, and is given orally twice daily for the entire duration of radiation therapy. Ganetespib will be started on Day 1 of radiation therapy and is administered as IV infusion over 1 hour on days 1, 8, 15 for cycle 1 and then on days 29 and 36 for cycle 2. In all patients, ganetespib monotherapy will be given up to 2 weeks prior to start of concurrent chemoradiation. Sequential biopsies will be taken at baseline and prior to the start of concurrent chemoradiation. In the dose escalation part of the study, the starting does of ganetespib is 60mg/m² once weekly, and capecitabine at a dose of 825 mg/m² twice daily.

Also known as: Ganetespib, STA-9090

capecitabine + ganetespib .

Eligibility Criteria

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

You may qualify if:

• Must be at least 18 years of age
• Stage II or III histologically-proven rectal adenocarcinoma. The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by proctoscopic examination.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Adequate hematologic function as defined by:
• Absolute neutrophil count ≥ 1,500 cells/µL
• Platelets ≥ 100,000/µL
• Hemoglobin ≥ 9.0g/dL
• Adequate hepatic function as defined by:
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Albumin ≥ 3.0 g/dL
• Adequate renal function as defined by:
• Serum creatinine ≤ 1.5 x ULN
• Calculated creatinine clearance of ≥ 50 mL/min
• International normalized ratio (INR) ≤ 1.5. Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level \< 1.1 U/mL are allowed on the trial.

You may not qualify if:

• History of previous radiation therapy to the abdomen or pelvis
• History of previous chemotherapy for rectal cancer
• Major surgery within 4 weeks prior to first dose of ganetespib
• Poor venous access for study drug administration. The study drug must be administered via peripheral venous access or through vascular access devices (VADs) (such as ports and peripherally-inserted central catheters \[PICCS\] containing silicone catheters. Use of VADs with catheters made of any other material is not allowed.
• History of severe allergic or hypersensitivity reactions to excipients (e.g., Polyethylene glycol \[PEG\] 300 and Polysorbate 80)
• Baseline corrected QT interval (QTc) \> 450 msec or previous history of QT prolongation while taking other medications
• Ventricular ejection fraction (Ef) ≤ 55% at baseline
• Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)
• Women who are pregnant or lactating
• Uncontrolled intercurrent illness
• Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
• Patients must be able to take oral medications.
• Unequivocal metastatic disease on computed tomography or chest X-ray
• Clinically significant comorbid conditions such as cardiovascular disease or significant peripheral vascular (e.g., uncontrolled hypertension, myocardial infarction, unstable angina) within 6 months of study entry, serious cardiac arrhythmia requiring medication, and uncontrolled infection.
• Clinical evidence of bleeding diathesis or coagulopathy

Sponsors & Collaborators

• Emory University: lead
• Synta Pharmaceuticals Corp.: collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Nagaraju GP, Park W, Wen J, Mahaseth H, Landry J, Farris AB, Willingham F, Sullivan PS, Proia DA, El-Hariry I, Taliaferro-Smith L, Diaz R, El-Rayes BF. Antiangiogenic effects of ganetespib in colorectal cancer mediated through inhibition of HIF-1alpha and STAT-3. Angiogenesis. 2013 Oct;16(4):903-17. doi: 10.1007/s10456-013-9364-7. Epub 2013 Jul 10.

  PMID: 23838996 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; STA 9090

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Bassel El-Rayes, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 13, 2012
• First Posted: March 15, 2012
• Study Start: May 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 22, 2016

Record last verified: 2016-02

Locations

US (1)