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Pemetrexed and TAS-102 in Combination With Bevacizumab in Refractory Colorectal Cancer

Primary Purpose

Colorectal Neoplasms

Status

Active

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Pemetrexed

TAS-102

Bevacizumab

About this trial

This is an interventional treatment trial for Colorectal Neoplasms

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
Subjects with metastatic colorectal cancer(CRC) (Stage IV).
Subjects must have failed at least two lines of prior treatment, which must include a fluoropyrimidine, oxaliplatin and irinotecan.
Subjects have failed or refused third-line treatment with regorafenib or fruquintinib.
Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy.
Subjects who have withdrawn from standard treatment due to unacceptable toxicity and precluding retreatment with the same agent prior to progression of disease will also be allowed.
Prior treatment with bevacizumab and/or cetuximab will be allowed, but the use of bevacizumab should be no more than one single line treatment.
Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
Life expectancy of at least 3 months.
Adequate bone marrow, liver, cardiac and renal function as assessed by the laboratory required by protocol.
Assigned informed consent.

Exclusion Criteria:

Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
Participants of other clinical trial within 4 weeks.
Diseases which will impact the absorption of TAS-102, eg. dysphagia, chronic diarrhea, bowl obstruction
Hemorrhage events of ≥grade 3 within 4 weeks.
Known central nervous system metastasis.
Uncontrolled hypertension. (Systolic blood pressure 140 mmHg or diastolic pressure 90 mmHg despite optimal medical management). Unstable angina,congestive heart failure,Myocardial infarction, Cardiac arrhythmias requiring anti-arrhythmic therapy.
Urine protein ≥++ and 24h urine protein more than 1.0g.
Chronically green wound or bone fracture.
Arterial or venous thrombotic or embolic events.
Tumor invading important blood vessel with high risk of severe hemorrhage.
Current active bleeding or any surgery taken within 2 months.
Abnormal coagulation function.
Thromboemboli events within 6 months.
Immune diseases or organ transplantation history.

Sites / Locations

the First Affiliated Hospital of Nanjing Medical University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pemetrexed + TAS-102 + Bevacizumab

Arm Description

Pemetrexed 500 mg/m2 d1+ TAS-102, capsule, 35mg/m2, bid,po, d1~5, d8~12 + Bevacizumab 5 mg/kg d1, d14; Repeated every 4 weeks

Outcomes

Primary Outcome Measures

Objective response rate(ORR)

The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)

Secondary Outcome Measures

Progression-free Survival(PFS)

PFS was defined as the time from assignment to disease progression radiological/clinical or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.

Overall Survival (OS)

OS is defined as the time from date of assignment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

Disease control rate (DCR)

DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD)

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

adverse events will be assessed according to CTCAE v4.0, including hematological and non-hematological adverse events. Non-hematological adverse events will be collected by patients reported outcomes questionaire. The adverse events of interest include hypertension,hand-foot syndrome,proteinuria,hoarseness,rash,etc.The dose reduction and drug discontinuance due to adverse events will also be recorded.

Full Information

NCT ID

NCT04683965

First Posted

December 22, 2020

Last Updated

July 31, 2022

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Collaborators

Jiangsu Hansoh Pharmaceutical Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04683965

Brief Title

Pemetrexed and TAS-102 in Combination With Bevacizumab in Refractory Colorectal Cancer

Official Title

A Single Arm, Open Label, Exploratory Study of Pemetrexed and TAS-102 in Combination With Bevacizumab in Patients Who Have Progressed After Standard Second Line Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

January 1, 2021 (Actual)

Primary Completion Date

January 1, 2024 (Anticipated)

Study Completion Date

May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The First Affiliated Hospital with Nanjing Medical University

Collaborators

Jiangsu Hansoh Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

5. Study Description

Brief Summary

Limited agents are optional after standard first and second line treatment for mCRC. Only Regorafenib and Fruquintinib are approved in China. PFS of these targeted drugs are not very long. Pemetrexed has shown significant efficacy in advanced lung cancer regarding PFS and OS with controllable toxicity. TAS-102 has been used in colorectal cancer with promising outcomes. Bevacizumab is also an important monoclonal antibody which could make benefits in treated patients. This study is aimed to explore the efficacy, safety in advanced colorectal cancer failed to standard therapy in Chinese population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pemetrexed + TAS-102 + Bevacizumab

Arm Type

Experimental

Arm Description

Pemetrexed 500 mg/m2 d1+ TAS-102, capsule, 35mg/m2, bid,po, d1~5, d8~12 + Bevacizumab 5 mg/kg d1, d14; Repeated every 4 weeks

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Intervention Description

Pemetrexed 500 mg/m2 d1

Intervention Type

Drug

Intervention Name(s)

TAS-102

Other Intervention Name(s)

LONSURF

Intervention Description

TAS-102, capsule, 35mg/m2, bid,p.o, d1~5,d8~12

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

Bevacizumab 5 mg/kg d1,d14

Primary Outcome Measure Information:

Title

Objective response rate(ORR)

Description

The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)

Time Frame

From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before November 1,2021

Secondary Outcome Measure Information:

Title

Progression-free Survival(PFS)

Description

Time Frame

From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before November 1,2021

Title

Overall Survival (OS)

Description

OS is defined as the time from date of assignment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

Time Frame

From assignment of the first subject until 40 death events observed, up to 2 years.

Title

Disease control rate (DCR)

Description

Time Frame

From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before November 1,2021

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Description

Time Frame

From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before November 1,2021

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded. Subjects with metastatic colorectal cancer(CRC) (Stage IV). Subjects must have failed at least two lines of prior treatment, which must include a fluoropyrimidine, oxaliplatin and irinotecan. Subjects have failed or refused third-line treatment with regorafenib or fruquintinib. Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy. Subjects who have withdrawn from standard treatment due to unacceptable toxicity and precluding retreatment with the same agent prior to progression of disease will also be allowed. Prior treatment with bevacizumab and/or cetuximab will be allowed, but the use of bevacizumab should be no more than one single line treatment. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. Life expectancy of at least 3 months. Adequate bone marrow, liver, cardiac and renal function as assessed by the laboratory required by protocol. Assigned informed consent. Exclusion Criteria: Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]. Participants of other clinical trial within 4 weeks. Diseases which will impact the absorption of TAS-102, eg. dysphagia, chronic diarrhea, bowl obstruction Hemorrhage events of ≥grade 3 within 4 weeks. Known central nervous system metastasis. Uncontrolled hypertension. (Systolic blood pressure 140 mmHg or diastolic pressure 90 mmHg despite optimal medical management). Unstable angina,congestive heart failure,Myocardial infarction, Cardiac arrhythmias requiring anti-arrhythmic therapy. Urine protein ≥++ and 24h urine protein more than 1.0g. Chronically green wound or bone fracture. Arterial or venous thrombotic or embolic events. Tumor invading important blood vessel with high risk of severe hemorrhage. Current active bleeding or any surgery taken within 2 months. Abnormal coagulation function. Thromboemboli events within 6 months. Immune diseases or organ transplantation history.

Facility Information:

Facility Name

the First Affiliated Hospital of Nanjing Medical University

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210029

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23679311

Citation

Wu XY, Huang XE, You SX, Lu YY, Cao J, Liu J. Phase II study of pemetrexed as second or third line combined chemotherapy in patients with colorectal cancer. Asian Pac J Cancer Prev. 2013;14(3):2019-22. doi: 10.7314/apjcp.2013.14.3.2019.

Results Reference

background

PubMed Identifier

28592624

Citation

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.

Results Reference

background

PubMed Identifier

30123359

Citation

Lim SW, Lee S, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK, Kim ST. Pemetrexed Monotherapy as Salvage Treatment in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy: A Phase II Single-arm Prospective Trial. J Cancer. 2018 Jul 30;9(16):2910-2915. doi: 10.7150/jca.24948. eCollection 2018.

Results Reference

background

PubMed Identifier

33313113

Citation

Yu Z, Wang J, Cai X, Gao Z, Wang S, Gu Y. Analysis of pemetrexed-based chemotherapy in the treatment of advanced colorectal cancer. Ann Transl Med. 2020 Nov;8(21):1368. doi: 10.21037/atm-20-1095.

Results Reference

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Pemetrexed and TAS-102 in Combination With Bevacizumab in Refractory Colorectal Cancer

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