Study of GVAX (With CY) and Pembrolizumab in MMR-p Advanced Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

Official title:

A Phase 2 Study of GVAX Colon Vaccine (With Cyclophosphamide) and Pembrolizumab in Patients With Mismatch Repair-Proficient (MMR-p) Advanced Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02981524
• Other study ID #: J16154
• Secondary ID: IRB00114053MISP5
• Status: Completed
• Phase: Phase 2
• Start date: May 26, 2017
• Est. completion date: March 20, 2018

Study information

• Verified date: February 2020
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will be looking at the objective response rate (ORR) as measured by RECIST in in patients with mismatch repair-proficient (MMR-p), advanced colorectal cancer that treated with CY/GVAX in combination with Pembrolizumab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: March 20, 2018
• Est. primary completion date: March 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Documented mismatch repair-proficient cancer of colorectum, who have received at least two prior lines of therapy for metastatic disease

2. Measurable disease by RECIST v1.1

3. Age >18 years

4. ECOG Performance Status of 0 to 1

5. Estimated life expectancy of greater than 3 months.

6. Adequate organ function as defined by study-specified laboratory tests

7. Must use acceptable form of birth control through the study and for 120 days after final dose of study drug

8. Signed informed consent form

9. Willing and able to comply with study procedures

Exclusion Criteria:

1. Has a known additional malignancy that is progressing or requires active treatment.

2. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.

3. Has known malignant small bowel obstruction within the last 6 months.

4. Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions.

5. Systemically active steroid use.

6. Has an active infection requiring systemic therapy.

7. Has a known history of active TB (Bacillus Tuberculosis).

8. Infection with HIV or hepatitis B or C.

9. Has history of (non-infectious) pneumonitis that required steroids.

10. Must not require supplemental oxygen or have a pulse oximetry < 92% on room air.

11. Conditions, including therapy, laboratory abnormalities, psychiatric or substance abuse disorders, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.

12. Pregnant or lactating.

13. Another investigational product within 28 days prior to receiving study drug.

14. Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug.

15. Chemotherapy, radiation, hormonal, or biological cancer therapy within 28 days prior to receiving study drug.

16. Has received a live vaccine within 30 days of planned start of study therapy.

17. Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).

18. Patients receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration.

19. Hypersensitivity to pembrolizumab or any of its excipients.

20. Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX vaccine.

21. Presence of any tissue or organ allograft and history of allogeneic hematopoietic stem cell transplant.

22. Unwilling or unable to comply with study procedures.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• CY
CY is administered intravenously at 200 mg/m2

Biological:
• GVAX
GVAX is administered intradermally at 5E8 colon cancer cells + 5E7 GM-CSF secreting

Drug:
• Pembrolizumab
Pembrolizumab is administered intravenously at 200 mg

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Yarchoan M, Huang CY, Zhu Q, Ferguson AK, Durham JN, Anders RA, Thompson ED, Rozich NS, Thomas DL 2nd, Nauroth JM, Rodriguez C, Osipov A, De Jesus-Acosta A, Le DT, Murphy AG, Laheru D, Donehower RC, Jaffee EM, Zheng L, Azad NS. A phase 2 study of GVAX col — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.	up to 1 year
Secondary	Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Number of participants who experience treatment related adverse events = grade 3 as defined by CTCAE 4.0.	up to 1 year
Secondary	Progression Free Survival (PFS)	Progression-free Survival (PFS) is defined as the number of days from cycle 1, day 1 of immunotherapy until first documented local progression or death due to any cause. PD is >20% increase in sum of diameters of target lesions as assessed using RECIST (version 1.1).	up to 1 year
Secondary	Overall Survival (OS)	OS is defined as the number of days from start of study treatment to time of death. Individuals will be censored at the date of the last study visit if no event occurs. The estimation method used was Kaplan-Meier.	Up to 1 year
Secondary	Duration of Response (DOR)	Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1, CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions.	1 year