Colorectal Cancer MetastaticPhase 2NCT01909830
Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients
A Phase 2 study testing Arm A : Gemcitabine + Pemetrexed in people with Colorectal Cancer Metastatic, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 1 site in Italy.
Trial summary
Study Design: Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination. Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks). Total duration of the study: 24 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- Arm A : Gemcitabine + Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2012to Mar 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic or cytologic confirmed diagnosis of colorectal carcinoma with metastatic (STAGE IV) disease.
- Measurable disease according to RECIST criteria
- Prior chemotherapy for metastatic disease is required; prior regimens (in adjuvant oral advanced stage setting) must include 5fluorouracile, Oxaliplatin and Irinotecan if not contraindicated.
- At least a 4-week interval between the last dose of chemotherapy and study registration.
- Recovery from all prior treatment-related toxicities to CTC <= grade 1 (except alopecia)
- Male or female, aged >= 18 years
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- Life expectancy of greater than 12 weeks.
- ECOG performance status <= 2
- Patients must have normal organ and marrow function as defined below:
- leukocytes >=3,000/microL
- absolute neutrophil count >=1,500/microL
- hemoglobin >= 9 g/dl
- platelets >=100,000/microL
- serum total bilirubin <= 1.5 X institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) <= 2.5 X institutional upper limit of normal (<= 5 times the upper institutional limits of normal if hepatic metastases are present)
- serum creatinine <= 1.5 times the institutional upper limits of normal
- Creatinine Clearance > 45 ml/min
- The effects of Gemcitabine and Pemetrexed on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception (hormonal or barrier method of birth control; abstinence) during the study and for 3 months thereafter. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Participant is willing and able to give informed consent for participation in the study. Voluntary signed and dated written informed consent form in accordance with regulatory and institutional guidelines obtained before the performance of any protocol-related procedures not part of normal patient care.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- Previous treatment with Gemcitabine or Pemetrexed.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Gemcitabine and/or Pemetrexed or other agents used in the study
- Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Past or current history of neoplasm other than colorectal carcinoma with a disease-free interval of less than 5 years, except for non-melanoma skin cancer or curatively treated carcinoma in situ of the cervix.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents 2 days before, the day of, and 2 days after the dose of pemetrexed single agent or pemetrexed plus carboplatin.
- HIV-positivity, whether or not symptomatic.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study to Evaluate Activity and Toxicity of Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients
Study Design:
Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination.
Read more
Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks).
Total duration of the study: 24 months.
Number of Subjects:
Approximately 38 subjects will be enrolled on study:
- First stage:12 patients enrolled
If 1 or 0 responses were observed, the trial had to be terminated:
- Second stage: an additional of 23 patients were to be enrolled. If 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.
Read the detailed description
A Phase II Study to evaluate activity and toxicity of Gemcitabine in Combination with Pemetrexed long term infusion in the Treatment of pretreated Metastatic Colorectal Cancer Patients
Study Design:
Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination.
Study Duration
Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks).
Total duration of the study: 24 months.
Primary objective:
- objective response rate (ORR: CR+PR+SD)
Secondary objectives:
- safety profile of the drugs combination;
- time to progression (TTP) and overall survival (OS)
Number of Subjects:
Approximately 38 subjects will be enrolled on study:
- First stage:12 patients enrolled
If 1 or 0 responses were observed, the trial had to be terminated:
- Second stage: an additional of 23 patients were to be enrolled. If 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.
Statistical Methodology:
A minimax two-stage Simon design will be employed. A 10% response will preclude further study, whereas a 30% response rate will indicate that further study would be warranted. Using α and β errors of 0.10 and 0.10, respectively, 12 patients will be enrolled in the first stage, and if 1 or 0 responses were observed, the trial had to be terminated. Otherwise, an additional of 23 patients were to be enrolled, and if 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.
The first 6 enrolled patients will be closely controlled for safety and further patients will be enrolled only in absence of severe toxicity resulting in discontinuation 1 month after the first cycle of the six patients.
The primary analysis will be performed on the ITT (Intention To Treat) population. PFS and OS will be estimated by the Kaplan-Meier method. The HR for PFS and OS will be estimated according to the Cox model, with its relative 95% confidence.
A secondary analysis will be performed on the PP (per-protocol) population. The Overall Response Rate to study treatment will be reported on the ITT and PP population with 95% confidence interval. Results will be tabulated and not evaluable patients will be included as additional category.
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- Arm A : Gemcitabine + Pemetrexed
- Keywords
- Colorectal Cancer Metastatic, pretreated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm A : Gemcitabine + PemetrexedDrug
Also called Gemcitabine, Pemetrexed
Gemcitabine: 1000 mg/m2 by intravenous infusion over an exact period of 30' (preferably by a pump to guarantee a constant speed of infusion) on day 3 of each cycle repeated every 14 days.
Pemetrexed: 150 mg/m2 by intravenous continuous infusion over an exact period of 8h on day 1 of each cycle repeated every 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Arm A : Gemcitabine + Pemetrexed | Experimental | Arm A : Gemcitabine: 1000 mg/m2 by intravenous infusion over an exact period of 30' (preferably by a pump to guarantee a constant speed of infusion) on day 3 of each cycle repeated every 14 days.
Pemetrexed: 150 mg/m2 by intravenous continuous infusion over an exact period of 8h on day 1 of each cycle repeated every 14 days. Receives: Drug: Arm A : Gemcitabine + Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Determination of the objective response rate (ORR: CR (complete response) +PR (partial response) +SD (stable disease)) of treated patients according to RECIST criteria
Measured: 2 years
Secondary outcomes (3)
safety profile of study treatment
Assessment of safety profile of study drug combination in patients treated: report of Adverse Events according to the The NCI's Common Toxicity Criteria version 4.0
Measured: 2 years
Time to Progression (TTP)
Determination of Time to Progression (TTP) of treated patients
Measured: 2 years
Overall Survival (OS)
Determination of Overall Survival (OS) of treated patients
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2013 (estimated)
- Study startJul 2012
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giovanni Luca Frassineti, MD, Principal investigator, IRST IRCCS, Meldola
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01909830
- Sponsor's protocol ID
- IRST153.03
- Other IDs
- 2010-019841-25
- Status last verified
- Jun 2015
- First submitted
- 19 Jun 2013
- Last updated
- 19 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Passardi A, Fanini F, Turci L, Foca F, Rosetti P, Ruscelli S, Casadei Gardini A, Valgiusti M, Dazzi C, Marangolo M. Prolonged Pemetrexed Infusion Plus Gemcitabine in Refractory Metastatic Colorectal Cancer: Preclinical Rationale and Phase II Study Results. Oncologist. 2017 Aug;22(8):886-e79. doi: 10.1634/theoncologist.2017-0206. Epub 2017 Jun 7.
PubMed 28592624
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Evaluate Activity and Toxicity of Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients
- ClinicalTrials.gov ID
- NCT01909830
- Acronym / sponsor ID
- IRST153.03
- Conditions
- Colorectal Cancer Metastatic
- Keywords
- Colorectal Cancer Metastatic, pretreated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 29 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study Design:
Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination.
Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks).
Total duration of the study: 24 months.
Number of Subjects:
Approximately 38 subjects will be enrolled on study:
- First stage:12 patients enrolled
If 1 or 0 responses were observed, the trial had to be terminated:
- Second stage: an additional of 23 patients were to be enrolled. If 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.
Detailed description
A Phase II Study to evaluate activity and toxicity of Gemcitabine in Combination with Pemetrexed long term infusion in the Treatment of pretreated Metastatic Colorectal Cancer Patients
Study Design:
Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination.
Study Duration
Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks).
Total duration of the study: 24 months.
Primary objective:
- objective response rate (ORR: CR+PR+SD)
Secondary objectives:
- safety profile of the drugs combination;
- time to progression (TTP) and overall survival (OS)
Number of Subjects:
Approximately 38 subjects will be enrolled on study:
- First stage:12 patients enrolled
If 1 or 0 responses were observed, the trial had to be terminated:
- Second stage: an additional of 23 patients were to be enrolled. If 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.
Statistical Methodology:
A minimax two-stage Simon design will be employed. A 10% response will preclude further study, whereas a 30% response rate will indicate that further study would be warranted. Using α and β errors of 0.10 and 0.10, respectively, 12 patients will be enrolled in the first stage, and if 1 or 0 responses were observed, the trial had to be terminated. Otherwise, an additional of 23 patients were to be enrolled, and if 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.
The first 6 enrolled patients will be closely controlled for safety and further patients will be enrolled only in absence of severe toxicity resulting in discontinuation 1 month after the first cycle of the six patients.
The primary analysis will be performed on the ITT (Intention To Treat) population. PFS and OS will be estimated by the Kaplan-Meier method. The HR for PFS and OS will be estimated according to the Cox model, with its relative 95% confidence.
A secondary analysis will be performed on the PP (per-protocol) population. The Overall Response Rate to study treatment will be reported on the ITT and PP population with 95% confidence interval. Results will be tabulated and not evaluable patients will be included as additional category.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm A : Gemcitabine + Pemetrexed | Experimental | Drug: Arm A : Gemcitabine + PemetrexedArm A : Gemcitabine: 1000 mg/m2 by intravenous infusion over an exact period of 30' (preferably by a pump to guarantee a constant speed of infusion) on day 3 of each cycle repeated every 14 days. Pemetrexed: 150 mg/m2 by intravenous continuous infusion over an exact period of 8h on day 1 of each cycle repeated every 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologic or cytologic confirmed diagnosis of colorectal carcinoma with metastatic (STAGE IV) disease.
- Measurable disease according to RECIST criteria
- Prior chemotherapy for metastatic disease is required; prior regimens (in adjuvant oral advanced stage setting) must include 5fluorouracile, Oxaliplatin and Irinotecan if not contraindicated.
- At least a 4-week interval between the last dose of chemotherapy and study registration.
- Recovery from all prior treatment-related toxicities to CTC <= grade 1 (except alopecia)
Key exclusion criteria (9 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- Previous treatment with Gemcitabine or Pemetrexed.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Gemcitabine and/or Pemetrexed or other agents used in the study
- Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm A : Gemcitabine + PemetrexedAlso: Gemcitabine, PemetrexedGemcitabine: 1000 mg/m2 by intravenous infusion over an exact period of 30' (preferably by a pump to guarantee a constant speed of infusion) on day 3 of each cycle repeated every 14 days. Pemetrexed: 150 mg/m2 by intravenous continuous infusion over an exact period of 8h on day 1 of each cycle repeated every 14 days. | Drug | Arm A : Gemcitabine + Pemetrexed |
Primary outcome
Objective Response Rate (ORR)
Time frame: 2 years
Determination of the objective response rate (ORR: CR (complete response) +PR (partial response) +SD (stable disease)) of treated patients according to RECIST criteria
3 secondary outcomes
safety profile of study treatment
Time frame: 2 years
Time to Progression (TTP)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2015.
- Derived from this study: PubMed 28592624Passardi A, Fanini F, Turci L, Foca F, Rosetti P, Ruscelli S, Casadei Gardini A, Valgiusti M, Dazzi C, Marangolo M. Prolonged Pemetrexed Infusion Plus Gemcitabine in Refractory Metastatic Colorectal Cancer: Preclinical Rationale and Phase II Study Results. Oncologist. 2017 Aug;22(8):886-e79. doi: 10.1634/theoncologist.2017-0206. Epub 2017 Jun 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giovanni Luca Frassineti, MD principal investigator
IRST IRCCS, Meldola
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Arm A : Gemcitabine + Pemetrexed in people with Colorectal Cancer Metastatic, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01909830, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2015.