Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer
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| ClinicalTrials.gov Identifier: NCT03579758 |
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Recruitment Status :
Recruiting
First Posted : July 9, 2018
Last Update Posted : May 3, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Stage I Gallbladder Cancer AJCC v8 Stage II Gallbladder Cancer AJCC v8 Stage IIA Gallbladder Cancer AJCC v8 Stage IIB Gallbladder Cancer AJCC v8 Stage III Gallbladder Cancer AJCC v8 Stage IIIA Gallbladder Cancer AJCC v8 Stage IIIB Gallbladder Cancer AJCC v8 | Drug: Capecitabine Drug: Cisplatin Drug: Gemcitabine | Phase 3 |
PRIMARY OBJECTIVE:
I. To determine the difference in overall survival (OS) at 3 years for patients with incidental gallbladder cancer (IGBC) who receive neoadjuvant gemcitabine hydrochloride (gemcitabine) and cisplatin (gem/cis) prior to reoperation followed by adjuvant capecitabine compared to patients who receive only adjuvant capecitabine after reoperation.
SECONDARY OBJECTIVES:
I. To determine the difference in recurrence-free survival (RFS) at 1 year for patients with IGBC who receive perioperative chemotherapy prior to and after re-operation compared to patients who receive only adjuvant chemotherapy after reoperation.
II. To assess the clinical effect of perioperative chemotherapy compared to only adjuvant chemotherapy after reoperation on resectability among 3 cohorts: all enrolled patients, all patients who undergo staging laparoscopy, and all patients who undergo laparotomy.
III. To compare the incidence of residual disease at the time of re-resection between patients who receive perioperative chemotherapy and those who receive only adjuvant chemotherapy.
OUTLINE: Participants are randomized to 1 of 2 arms.
ARM I: Participants undergo re-resection (including partial liver resection and portal lymph node dissection) after incidental diagnosis of gallbladder cancer. Participants then receive capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Participants receive cisplatin intravenously (IV) over 1 hour and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Within 10 weeks of chemotherapy, participants undergo re-resection (including partial liver resection and portal lymph node dissection). Participants then receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up periodically for up to 3 years.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 264 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Perioperative Chemotherapy Prior To and After Reoperation for Incidental Gallbladder Cancer - An International, Randomized Phase III Trial |
| Actual Study Start Date : | April 3, 2019 |
| Estimated Primary Completion Date : | April 30, 2026 |
| Estimated Study Completion Date : | April 30, 2026 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm I (capecitabine)
Participants undergo re-resection (including partial liver resection and portal lymph node dissection). Participants then receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
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Drug: Capecitabine
Given PO
Other Names:
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Experimental: Arm II (chemotherapy, capecitabine)
Participants receive cisplatin IV over 1 hour and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Within 10 weeks of chemotherapy, participants undergo re-resection (including partial liver resection and portal lymph node dissection). Participants then receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
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Drug: Capecitabine
Given PO
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Gemcitabine Given IV
Other Names:
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- Overall survival [ Time Frame: Up to 3 years after study start ]Overall survival (OS) is defined as time from randomization to death from any cause.
- Recurrence-free survival [ Time Frame: From surgery to first observed disease recurrence or death from any cause, assessed at 1 year ]Recurrence-free survival (RFS) at one year, defined as time from surgery to first observed disease recurrence or death from any cause, among only patients who undergo complete, curative-intent re-resection. Disease recurrence will be based on findings from surveillance cross-sectional imaging of the chest, abdomen, and pelvis (CT or MRI, and any other additional imaging necessary to confirm recurrence). Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be excluded from the RFS analysis
- Overall resectability rate [ Time Frame: Up to 3 years after study start ]Overall resectability rate is defined as the proportion of patients who successfully undergo a re-resection versus all enrolled patients. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.
- Resectability rate at diagnostic laparoscopy [ Time Frame: Up to 3 years after study start ]Resectability rate at diagnostic laparoscopy is defined as the proportion of patients who successfully undergo a re-resection versus all patients who undergo staging laparoscopy. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.
- Resectability rate at laparotomy [ Time Frame: Up to 3 years after study start ]Resectability rate at laparotomy is defined as the proportion of patients who successfully undergo a re-resection versus all patients who undergo laparotomy. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.
- Incidence of residual disease after or at the time of re-resection [ Time Frame: Up to 3 years after study start ]Incidence of residual disease after or at the time of re-resection is defined as the presence of either microscopic or gross malignancy based on pathologic analysis.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically-confirmed T1b, T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
- Resectable disease at the time of enrollment based on high-quality, preoperative, cross-sectional imaging of the chest, abdomen, and pelvis (C/A/P)
- Enrollment and randomization within 12 weeks of initial cholecystectomy
- High-quality cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) performed within 4 weeks prior to enrollment
- Able to give informed consent
- Able to adhere to study visit schedule and other protocol requirements
- Eastern Cooperative Oncology Group (ECOG) performance status of < 2
- Absolute neutrophil count ≥ 1500/mm³
- Platelet count ≥ 100,000/mm³
Exclusion Criteria:
- Patients with histologically-confirmed Tis, T1a, or T4 tumors
- Unresectable gallbladder cancer at the time of enrollment based on high-quality, preoperative, cross-sectional imaging of the C/A/P
- Unable to sign informed consent
- Serum creatinine > 1.5 x upper limit of normal or estimated creatinine clearance (CrCl) < 45 ml/min
- Serum total bilirubin > 1.5 x upper limit of normal
- Presence of active infection
- Pregnant and/or breastfeeding
- Known dihydropyrimidine dehydrogenase deficiency
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03579758
| Contact: Shishir K. Maithel, MD | 404-778-5777 | smaithe@emory.edu |
| United States, California | |
| Stanford Cancer Institute Palo Alto | Recruiting |
| Stanford, California, United States, 94304 | |
| Contact: Shishir Maithel, MD 404-778-5777 smaithe@emory.edu | |
| United States, Georgia | |
| Emory University Hospital Midtown | Recruiting |
| Atlanta, Georgia, United States, 30308 | |
| Contact: Swathi Chinaranagari 404-686-0239 swathi.chinaranagari@emory.edu | |
| Contact: Shabnam Montazeri 404-686-0242 shabnam.montazeri@emory.edu | |
| Principal Investigator: Shishir Maithel, MD | |
| Emory University Hospital/Winship Cancer Institute | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Sheena Abraham 404-778-2670 sheena.abraham@emory.edu | |
| Principal Investigator: Shishir Maithel, MD | |
| Emory Saint Joseph's Hospital | Recruiting |
| Atlanta, Georgia, United States, 30342 | |
| Contact: Alicia Escobar 678-843-7029 alicia.m.escobar@emory.edu | |
| Contact: Krystal Reese 678-843-5911 krystal.reese@emory.edu | |
| Principal Investigator: Shishir Maithel, MD | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center | Recruiting |
| New York, New York, United States, 10065 | |
| Contact: Shishir Maithel, MD 404-778-5777 smaithe@emory.edu | |
| Principal Investigator: | Shishir K. Maithel, MD | Emory University |
| Responsible Party: | Shishir Kumar Maithel, Principal Investigator, Emory University |
| ClinicalTrials.gov Identifier: | NCT03579758 History of Changes |
| Other Study ID Numbers: |
IRB00103908 NCI-2018-00816 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) EU4338-18 ( Other Identifier: Emory University Hospital/Winship Cancer Institute ) |
| First Posted: | July 9, 2018 Key Record Dates |
| Last Update Posted: | May 3, 2019 |
| Last Verified: | May 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Gallbladder Neoplasms Biliary Tract Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Biliary Tract Diseases Digestive System Diseases Gallbladder Diseases Gemcitabine Cisplatin Capecitabine |
Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |