5-Fluorouracil Followed by Interferon-alfa-2b in Previously-treated Metastatic Gastrointestinal, Kidney, or Lung Cancer

Phase II Trial of Chemoimmunotherapy With 5-Fluorouracil Followed by Interferon-alfa-2b in Previously-treated Metastatic Gastrointestinal, Kidney, or Lung Cancer

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01658813

Enrollment

Registered

2012-08-07

Start date

2012-07-31

Completion date

2014-07-31

Last updated

2018-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gastrointestinal Cancer Metastatic, Non Small Cell Lung Cancer Metastatic, Renal Cell Cancer Metastatic

Keywords

Metastatic Gastrointestinal, Metastatic Kidney, Metastatic Lung

Brief summary

The purpose of this study is to determine whether the combination of a 5-Fluorouracil (5-FU) and interferon, which is able to stimulate the immune system to kill cancer cells, will help to increase tumor shrinkage in previously-treated metastatic gastrointestinal, kidney, or lung Cancer.

Detailed description

Interferon with continuous infusion 5-Fluorouracil (5-FU) regimens have shown response rates ranging from 0-43% in various cancers. Monthly bolus 5-FU + interferon-alfa-2b has not undergone formal phase II testing. In a small pilot study, a 5 consecutive day schedule of 5-FU and interferon-alfa-2b resulted in the limiting toxicities of diarrhea and mucositis. A more limited schedule was recommended. Therefore, it is reasonable to examine such a schedule. In the current study, 5-FU will be followed by interferon-alfa-2b daily for 3 days to attempt to benefit from both the biochemical and immunologic mechanisms described above.

Interventions

DRUG5-Fluorouracil and Interferon

5-Fluorouracil Interferon-alfa-2b

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patients must have histologically-proven, metastatic gastrointestinal, kidney, or lung cancer who have had disease progression on at least two prior systemic therapies. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 and estimated survival of at least 3 months. * Patients must be felt to have recovered from effects of prior therapy, such as past expected white blood count nadir for chemotherapy (\> 2 weeks for most agents, \> 6 weeks for nitrosoureas or mitomycin-C) * Patient consent must be obtained prior to entrance onto study. * White blood count \> 3500/mm3; platelet count of at least 100,000/mm3; hemoglobin \> 9.0 gm/dl; bilirubin, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) less than 3 times the upper limit of normal; serum creatinine \< 1.8. * Corticosteroids and immunosuppressive agents are not permitted during the course of the study. Patients must have received no corticosteroids or immunosuppressive medications at least 2 weeks prior to entrance on-study. * Patients with elevated temperatures \> 100.5 degrees F, must have sources of occult infection excluded. * Women of childbearing potential must have a negative pregnancy test and must take adequate precautions to prevent pregnancy during treatment.

Exclusion criteria

* Evidence of significant cardiovascular disease including history of recent (\< 6 months) myocardial infarction, uncompensated congestive heart failure, primary cardiac arrhythmias (not due to electrolyte disorder or drug toxicity, for example) beyond occasional PVC's, angina, or cerebrovascular accident. * Prior history of psychiatric disorder that could be exacerbated by interferon therapy or which could preclude completion of this therapy. * Pregnancy or lactation. * History of hypersensitivity to interferon alfa or fluoropyrimidines. * History of severe debilitating pulmonary disease, such as chronic obstructive pulmonary disease requiring continuous oxygen therapy. * History of autoimmune disease requiring immunosuppression. * Documented inflammatory joint or systemic inflammatory disease (such as Lupus) which could be exacerbated by interferon therapy.

Design outcomes

Primary

Measure	Time frame	Description
Progression Free Survival	Assessed up to 2 years	Progression Free Survival (PFS) was calculated as the time (months) from date of the start of treatment to the date of first observed disease progression (per standard Response Evaluation Criteria In Solid Tumors \[RECIST\] or date of death from any cause, whichever came first, assessed up to 2 years. The actual date of tumor assessments was used for this calculation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.

Secondary

Measure	Time frame	Description
Number of Responses	up to 2 years.	Radiographic studies to evaluate for response were done at 8 weeks (after 1 cycle). Standard RECIST response criteria were utilized. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Response Rate	up to 2 years	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by radiographic imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Median Duration of Response	Up tp 2 years	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by radiographic imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Median Survival	up to 2 years	Median survival was measured from date of entry on study until date of death

Countries

United States

Participant flow

Participants by arm

Arm	Count
Number of Participants 5-Fluorouracil and Interferon-alfa-2b	18
Total	18

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Disease progression	3

Baseline characteristics

Characteristic	Number of Participants
Age, Continuous	57 years
Region of Enrollment United States	18 participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	12 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	18 / 18
serious Total, serious adverse events	0 / 18

Outcome results

Primary

Progression Free Survival

Progression Free Survival (PFS) was calculated as the time (months) from date of the start of treatment to the date of first observed disease progression (per standard Response Evaluation Criteria In Solid Tumors \[RECIST\] or date of death from any cause, whichever came first, assessed up to 2 years. The actual date of tumor assessments was used for this calculation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.

Time frame: Assessed up to 2 years