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

NCT ID: NCT02981524

Last Updated: 2021-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-26
• Study Completion Date: 2018-03-20

Brief 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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CY/GVAX with Pembrolizumab

During each 21 day cycles, Cyclophosphamide (CY) is administered on Day 1 at 200 mg/m2 followed by Pembrolizumab at 200mg, the colon cancer vaccine (GVAX) is administered on Day 2 at 5E8 colon cancer cells + 5E7 GM-CSF secreting cells for the first 4 cycles of treatment. After cycle 4, cyclophosphamide and GVAX will be administered with every 4th cycle.

Group Type: EXPERIMENTAL

CY

Intervention Type: DRUG

CY is administered intravenously at 200 mg/m2

GVAX

Intervention Type: BIOLOGICAL

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

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is administered intravenously at 200 mg

Interventions

CY

CY is administered intravenously at 200 mg/m2

Intervention Type: DRUG

GVAX

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

Intervention Type: BIOLOGICAL

Pembrolizumab

Pembrolizumab is administered intravenously at 200 mg

Intervention Type: DRUG

Other Intervention Names

Cyclophosphamide, Cytoxan; Colon cancer vaccine; KEYTRUDA, MK-3475

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nilofer Azad, MD

Role: PRINCIPAL_INVESTIGATOR

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

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 colon vaccine with cyclophosphamide and pembrolizumab in patients with mismatch repair proficient advanced colorectal cancer. Cancer Med. 2020 Feb;9(4):1485-1494. doi: 10.1002/cam4.2763. Epub 2019 Dec 26.

Reference Type: RESULT

PMID: 31876399 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00114053

Identifier Type: OTHER

Identifier Source: secondary_id

MISP53919

Identifier Type: OTHER

Identifier Source: secondary_id

J16154

Identifier Type: -

Identifier Source: org_study_id