Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients

NCT01909830 | Completed Phase 2

• 2 other identifiers: IRST153.032010-019841-25
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Colorectal Cancer Metastatic

Keywords

Colorectal Cancer Metastatic; pretreated

Outcome Measures

Primary Outcomes (1)

• 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

  2 years

Secondary Outcomes (3)

• safety profile of study treatment

  2 years

• Time to Progression (TTP)

  2 years

• Overall Survival (OS)

  2 years

Study Arms (1)

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.

Drug: Arm A : Gemcitabine + Pemetrexed

Interventions

Arm A : Gemcitabine + Pemetrexed DRUG

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.

Also known as: Gemcitabine, Pemetrexed

Arm A : Gemcitabine + Pemetrexed

Eligibility Criteria

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

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead

Study Sites (1)

UO Oncologia Medica IRCCS IRST

Meldola (FC), FC, 47014, Italy

Location

Related Publications (1)

• 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.

  PMID: 28592624 DERIVED

MeSH Terms

Interventions

Pemetrexed; Gemcitabine

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Giovanni Luca Frassineti, MD

  IRST IRCCS, Meldola

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: July 29, 2013
• Study Start: July 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: June 19, 2015

Record last verified: 2015-06

Locations

IT (1)