A Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer

NCT01729923 | Terminated Phase 2 Results

• 3 other identifiers: 7707NCI-2012-02137P30CA015704
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well capecitabine and celecoxib with or without radiation therapy works in treating patients with colorectal cancer that is newly diagnosed or has been previously treated with fluorouracil, and has spread to other parts of the body (metastatic). Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving capecitabine and celecoxib together with radiation therapy may kill more tumor cells.

Conditions

Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of CR, Assessed According to CEA and CA 19-9 Measurements and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level in response to ADAPT therapy.

  3 years

Secondary Outcomes (6)

• Best Overall Response Rate Among All Patients Who Had RECIST Measurements at Baseline and at Least One Subsequent Occasion

  Serial measures at 9 week intervals up to 5 years

• Best Overall Response Rate Among All Patients Who Had RECIST Measurements at Baseline and at Least One Subsequent Occasion and Did Not Have Surgery or Radiation Therapy

  Serial measures at 9 week intervals up to 5 years

• K-ras Mutation Status

  Up to 5 years

• Overall Survival

  Until death or last reported survival, up to 5 years

• Quality of Life (QOL), Assessed Using the M.D. Anderson Symptom Inventory (MDASI)

  Up to 5 years

Study Arms (1)

Treatment (capecitabine, celecoxib, radiation therapy)

EXPERIMENTAL

Patients proceed to surgery, radiation therapy with ADAPT therapy followed by maintenance ADAPT therapy, or ADAPT therapy. Eligible patients undergo surgical resection at baseline or upon achievement of resectable disease after radiation therapy. RADIATION + ADAPT: Patients undergo radiation therapy 5 days per week and receive capecitabine PO BID and celecoxib PO BID 5 days per week during radiation. ADAPT: Patients receive capecitabine PO BID on days 1-14 and celecoxib PO BID on days 1-21. Courses repeat every 21 days for up to 3 years in the absence of disease progression or unacceptable toxicity.

Drug: Capecitabine; Drug: Celecoxib; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Radiation: Stereotactic Radiosurgery; Procedure: Therapeutic Conventional Surgery

Interventions

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Treatment (capecitabine, celecoxib, radiation therapy)

Celecoxib DRUG

Given PO

Also known as: Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177

Treatment (capecitabine, celecoxib, radiation therapy)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (capecitabine, celecoxib, radiation therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (capecitabine, celecoxib, radiation therapy)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (capecitabine, celecoxib, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (capecitabine, celecoxib, radiation therapy)

Stereotactic Radiosurgery RADIATION

Undergo stereotactic radiosurgery

Also known as: Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery

Treatment (capecitabine, celecoxib, radiation therapy)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection

Treatment (capecitabine, celecoxib, radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed colorectal cancer
• Evaluable or measurable radiographic evidence of colorectal cancer
• Patients with unresected metastases from colorectal cancer; patients may be either untreated with chemotherapy or currently receiving first-line 5-FU based chemotherapy (folinic acid-fluorouracil-irinotecan hydrochloride \[FOLFIRI\], capecitabine-irinotecan hydrochloride \[CAPIRI\], fluorouracil-leucovorin calcium-oxaliplatin \[FOLFOX\], or capecitabine-oxaliplatin \[CAPOX\] with or without bevacizumab) within 10 months of beginning ADAPT therapy with at least stable disease radiographically; patients who received prior adjuvant chemotherapy with 5-FU, capecitabine, or FOLFOX are eligible if adjuvant therapy was completed greater than 6 months ago
• History of histological confirmation for recurrent disease, or if recurrent disease is not readily accessible to biopsy, must have two consecutive carcinoembryonic antigen (CEA) or cancer antigen (CA) 19-9 increases, or positron emission tomography (PET) avidity
• Men and women from all ethnic and racial groups
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Total bilirubin =\< 1.5 x the institutional upper-normal limit (IUNL)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and/or alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x IUNL
• Alkaline phosphatase =\< 2.5 x IUNL
• Leukocytes \>= 3,000/uL
• Absolute neutrophil count \>= 1,000/uL
• Platelets \>= 100,000/uL
• Women of childbearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to beginning ADAPT therapy and for the duration of study participation
• Negative urine pregnancy test for women of childbearing potential
• Must have the ability to understand and the willingness to provide a written informed consent to participate in the study

You may not qualify if:

• History of allergies to sulfonamide, aspirin, any nonsteroidal anti-inflammatory drugs (NSAIDS), 5-FU or celecoxib
• Prior 5-FU-based adjuvant chemotherapy less than 6 months prior to beginning ADAPT therapy and any residual neuropathy \> grade 2
• Any regular use of cyclooxygenase-2 (COX-2) inhibitors as defined by 2-3 times per week
• Pregnant or lactating women
• History of significant neurologic or psychiatric disorders, including dementia or seizures that would impede consent, treatment, or follow up
• Any serious illness or medical condition that could affect participation on trial
• Any uncontrolled congestive heart failure New York Heart Association class III or IV
• Any uncontrolled hypertension, arrhythmia, or active angina pectoris
• Any history of major myocardial infarction, stroke or transient ischemic attack (TIA); minor acute myocardial infarction (AMI) and patients who have had cardiac bypass free of symptoms for at least 2 years may be eligible at the discretion of the study chair
• Serious uncontrolled active infection
• Patients with creatinine clearance: \< 50 mL/min are excluded from this protocol; capecitabine is contraindicated in severe renal impairment (clearance \< 40 mL/min)
• Inability to swallow oral medications or any medical conditions that may affect intestinal absorption of the study agent or inability to comply with oral medication
• Use of warfarin is not allowed; patient is recommended to switch to low molecular weight heparin (LMWH) before participating in this study
• Patients with any history of brain or bone metastasis or who have developed progressive disease on first line 5-FU based therapy
• Current use of systemic steroid medication

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Capecitabine; Celecoxib; Radiotherapy, Intensity-Modulated; Radiotherapy; Radiation; Radiosurgery

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic 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; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Therapeutics; Physical Phenomena; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Stacey Cohen, Principal Investigator
• Organization: University of Washington

shiovitz@uw.edu

206-606-6658

Study Officials

• Stacey Cohen

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: November 15, 2012
• First Posted: November 20, 2012
• Study Start: March 1, 2013
• Primary Completion: September 6, 2016
• Study Completion: September 6, 2016
• Last Updated: January 16, 2018
• Results First Posted: December 2, 2017

Record last verified: 2017-12

Locations

US (1)