A Phase 2 interventional study of Capecitabine and Carboplatin in Gastric Neuroendocrine Carcinoma, Intestinal Neuroendocrine Carcinoma and Pancreatic Neuroendocrine Carcinoma, sponsored by ECOG-ACRIN Cancer Research Group. Active, not recruiting at 673 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-02.
Sponsored by ECOG-ACRIN Cancer Research Group · Phase 2, Interventional, and Treatment
This randomized phase II trial studies how well temozolomide and capecitabine work compared to standard treatment with cisplatin or carboplatin and etoposide in treating patients with neuroendocrine carcinoma of the gastrointestinal tract or pancreas that has spread to other parts of the body (metastatic) or cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, capecitabine, cisplatin, carboplatin and etoposide, 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. Certain types of neuroendocrine carcinomas may respond better to treatments other than the current standard treatment of cisplatin and etoposide. It is not yet known whether temozolomide and capecitabine may work better than cisplatin or carboplatin and etoposide in treating patients with this type of neuroendocrine carcinoma, called non-small cell neuroendocrine carcinoma.
PRIMARY OBJECTIVES:
I. To assess the progression free survival (PFS) of platinum (cisplatin or carboplatin) and etoposide versus the PFS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
SECONDARY OBJECTIVES:
I. To assess the response rate (RR) of platinum (cisplatin or carboplatin) and etoposide versus the RR of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
II. To assess the overall survival (OS) of platinum (cisplatin or carboplatin) and etoposide versus the OS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
III. To evaluate the toxicities associated with the combination of temozolomide and capecitabine and the combination of platinum (cisplatin or carboplatin) and etoposide, respectively, in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
TERTIARY OBJECTIVES:
I. To assess the impact of each treatment regimen on PFS, RR and OS based on marker of proliferation Ki-67 index in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. (Laboratory) II. To assess the prognostic significance of well differentiated versus poorly differentiated non-small cell gastroenteropancreatic neuroendocrine tumors in relationship to survival and response to treatment. (Laboratory) III. To assess the agreement in Ki-67 status between that reported by institutional pathologist and that reported by central pathology review. (Laboratory)
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14 and temozolomide PO once daily (QD) on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive cisplatin intravenously (IV) on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
20 studies on the registry are indexed under Somatostatinoma; 2 are open to participants now.
This study's enrollment of 67 is above the median of 52 across 17 interventional studies indexed under Somatostatinoma.
Browse Somatostatinoma studies →ECOG-ACRIN Cancer Research Group is the lead sponsor of 118 studies on the registry; 13 are open to participants now.
Of its 13 completed or terminated interventional studies of FDA-regulated products, 13 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; baseline measurements and evaluations of all sites of disease must be obtained within 4 weeks prior to randomization and must be acquired by multiphasic computed tomography (CT) or contrast magnetic resonance imaging (MRI)
Serum creatinine =\< 1.5 X institutional ULN and creatinine clearance >= 60 ml/min
Exclusion Criteria:
Patients with a history of the following within =\< 12 months of study entry are not eligible:
Patients must NOT have previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:
Women must not be pregnant or breast-feeding
Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Capecitabine · Other: Laboratory Biomarker Analysis · Drug: Temozolomide
Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Carboplatin · Drug: Cisplatin · Drug: Etoposide · Other: Laboratory Biomarker Analysis
Given PO
Also known as: Xeloda, ACH-Capecitabine, Mint-Capecitabine, SANDOZ Capecitabine, TARO-Capecitabine, EVA-Capecitabine
Given IV
Also known as: Paraplatin
Given IV
Also known as: Platinol-AQ
Given IV
Also known as: VP-16 or VP-16-213
Correlative studies
Also known as: VePesid®
Given PO
Also known as: Toposar®
Progression-free Survival (PFS)
PFS is defined as the time from randomization to documented progression or death without progression. PFS is censored at the date of last disease evaluation. The study was closed for futility in 2021 after the 2021 Spring DSMC meeting, which found that the boundary for futility had been met (ie, temozolomide and capecitabine did not appear to be superior to platinum and etoposide chemotherapy). As the interim analysis finding led to the conclusion of the study, no PFS stratified logrank test was conducted with the data extracted on April 23rd, 2025 for the final analysis, that was presented here.
Time frame: assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years from randomization until disease progression, up to 5 years from study registration
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause. OS is censored at the date of last contact. Median OS is estimated using the Kaplan-Meier method.
Time frame: assessed at baseline, then every 3 months within 2 years from randomization, and every 6 months if patient is 3-5 years from randomization, up to 5 years from randomization
Objective Response Rate (ORR)
ORR is defined as the proportion of patients with complete response (CR) or partial response (PR). Response is evaluated using the RECIST 1.1 criteria. CR is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years, up to 5 years from registration; the best response among all assessments was considered as objective response
To Assess the Objective Response Rate Based on Marker of Proliferation Ki-67 Index
The impact of each treatment regimen on objective response rate (ORR, defined as above in the secondary objective) are assessed by Ki-67 index level as an exploratory analysis. Using Youden's index, which considers specificity and sensitivity equally important, the optimal cutoff point of Ki-67 index to best predict response is 50.5. Using the optimal Ki-67 cutoff value of 50.5 from the ROC analysis, patients were divided into Ki-67 low (Ki-67 \< 50.5) and high (Ki-67 ≥ 50.5) groups. The impact of each treatment regimen on ORR was explored in Ki-67 low and Ki-67 high separately.
Time frame: assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years, up to 5 years from registration; the best response among all assessments was considered as objective response
To Assess the Treatment Effect Based on Marker of Proliferation Ki-67 Index
The impact of each treatment regimen on PFS and OS (defined as above in the primary and secondary objectives) are assessed by Ki-67 index level as an exploratory analysis. Using Youden's index, which considers specificity and sensitivity equally important, the optimal cutoff point of Ki-67 index to best predict response is 50.5. Using the optimal Ki-67 cutoff value of 50.5 from the ROC analysis, patients were divided into Ki-67 low (Ki-67 \< 50.5) and high (Ki-67 ≥ 50.5) groups. The impact of each treatment regimen on PFS and OS were explored in Ki-67 low and Ki-67 high separately.
Time frame: assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years from randomization until disease progression, up to 5 years from study registration
Association Between Tumor Differentiation and Treatment Effect
The association between tumor differentiation (well differentiated versus poorly differentiated) with PFS, ORR and OS (defined as in the primary and secondary objectives) were evaluated.
Time frame: assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years from randomization until disease progression, up to 5 years from study registration
The study was activated on November 6th, 2015 and closed to accrual on April 1st, 2021 with final accrual of 67 patients.
| Milestone | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) |
|---|---|---|
| Started | 32 | 35 |
| Eligible | 31 | 32 |
| Started protocol therapy | 28 | 29 |
| Completed | 0 | 0 |
| Not completed | 32 | 35 |
| Withdrew: Disease progression | 17 | 15 |
| Withdrew: Adverse event | 5 | 7 |
| Withdrew: Withdrawal by subject | 2 | 5 |
| Withdrew: Physician decision | 1 | 2 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Alternative therapy | 2 | 0 |
| Withdrew: Never start protocol therapy | 4 | 6 |
PFS is defined as the time from randomization to documented progression or death without progression. PFS is censored at the date of last disease evaluation. The study was closed for futility in 2021 after the 2021 Spring DSMC meeting, which found that the boundary for futility had been met (ie, temozolomide and capecitabine did not appear to be superior to platinum and etoposide chemotherapy). As the interim analysis finding led to the conclusion of the study, no PFS stratified logrank test was conducted with the data extracted on April 23rd, 2025 for the final analysis, that was presented here.
| months | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) |
|---|---|---|
| Progression-free Survival (PFS) | 3.1 (2.1 to 8.4) | 5.5 (4.0 to 8.0) |
OS is defined as the time from randomization to death from any cause. OS is censored at the date of last contact. Median OS is estimated using the Kaplan-Meier method.
| months | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) |
|---|---|---|
| Overall Survival (OS) | 12.6 (5.4 to 30.3) | 10.8 (9.6 to 21.1) |
ORR is defined as the proportion of patients with complete response (CR) or partial response (PR). Response is evaluated using the RECIST 1.1 criteria. CR is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
| percentage of participants | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) |
|---|---|---|
| Objective Response Rate (ORR) | 19 (7 to 37) | 31 (16 to 50) |
The impact of each treatment regimen on objective response rate (ORR, defined as above in the secondary objective) are assessed by Ki-67 index level as an exploratory analysis. Using Youden's index, which considers specificity and sensitivity equally important, the optimal cutoff point of Ki-67 index to best predict response is 50.5. Using the optimal Ki-67 cutoff value of 50.5 from the ROC analysis, patients were divided into Ki-67 low (Ki-67 \< 50.5) and high (Ki-67 ≥ 50.5) groups. The impact of each treatment regimen on ORR was explored in Ki-67 low and Ki-67 high separately.
| percentage of participants | Arm A (Capecitabine, Temozolomide) -- Ki-67 Low | Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 Low | Arm A (Capecitabine, Temozolomide) -- Ki-67 High | Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 High |
|---|---|---|---|---|
| To Assess the Objective Response Rate Based on Marker of Proliferation Ki-67 Index | 25.0 (8.7 to 49.1) | 35.7 (12.8 to 64.9) | 9.1 (0.2 to 41.3) | 27.8 (9.7 to 53.5) |
The impact of each treatment regimen on PFS and OS (defined as above in the primary and secondary objectives) are assessed by Ki-67 index level as an exploratory analysis. Using Youden's index, which considers specificity and sensitivity equally important, the optimal cutoff point of Ki-67 index to best predict response is 50.5. Using the optimal Ki-67 cutoff value of 50.5 from the ROC analysis, patients were divided into Ki-67 low (Ki-67 \< 50.5) and high (Ki-67 ≥ 50.5) groups. The impact of each treatment regimen on PFS and OS were explored in Ki-67 low and Ki-67 high separately.
Results for this outcome have not been posted.
The association between tumor differentiation (well differentiated versus poorly differentiated) with PFS, ORR and OS (defined as in the primary and secondary objectives) were evaluated.
Results for this outcome have not been posted.
Collected over Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A (Capecitabine, Temozolomide) | 23/31 (74.2%) | 9/28 (32.1%) | 27/28 (96.4%) |
| Arm B (Cisplatin, Carboplatin, Etoposide) | 25/32 (78.1%) | 20/29 (69%) | 28/29 (96.6%) |
| Event | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) |
|---|---|---|
| Neutrophil count decreasedInvestigations | 2/28 | 13/29 |
| AnemiaBlood and lymphatic system disorders | 1/28 | 8/29 |
| White blood cell decreasedInvestigations | 2/28 | 6/29 |
| Platelet count decreasedInvestigations | 1/28 | 5/29 |
| Febrile neutropeniaBlood and lymphatic system disorders | 2/28 | 3/29 |
| Abdominal painGastrointestinal disorders | 2/28 | 0/29 |
| DiarrheaGastrointestinal disorders | 2/28 | 0/29 |
| NauseaGastrointestinal disorders | 2/28 | 0/29 |
| SepsisInfections and infestations | 2/28 | 1/29 |
| DehydrationMetabolism and nutrition disorders | 2/28 | 0/29 |
| Event | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) |
|---|---|---|
| AnemiaBlood and lymphatic system disorders | 10/28 | 23/29 |
| FatigueGeneral disorders and administration site conditions | 18/28 | 18/29 |
| AlopeciaSkin and subcutaneous tissue disorders | 1/28 | 18/29 |
| NauseaGastrointestinal disorders | 15/28 | 14/29 |
| Platelet count decreasedInvestigations | 8/28 | 14/29 |
| White blood cell decreasedInvestigations | 7/28 | 12/29 |
| Neutrophil count decreasedInvestigations | 4/28 | 11/29 |
| VomitingGastrointestinal disorders | 8/28 | 8/29 |
| DiarrheaGastrointestinal disorders | 7/28 | 5/29 |
| HypokalemiaMetabolism and nutrition disorders | 1/28 | 7/29 |
Eligible patients
| Age, Continuous(years) | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) | Total |
|---|---|---|---|
| Median | 66 (28 to 81) | 62 (34 to 77) | 65 (28 to 81) |
| Sex: Female, Male(Participants) | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) | Total |
|---|---|---|---|
| Female | 11 | 14 | 25 |
| Male | 20 | 18 | 38 |
| Race (NIH/OMB)(Participants) | Arm A (Capecitabine, Temozolomide) | Arm B (Cisplatin, Carboplatin, Etoposide) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 1 |
| Black or African American | 1 | 2 | 3 |
| White | 27 | 26 | 53 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 1 | 4 |
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