AlloStim® In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer

NCT01741038 | Withdrawn Phase 2 DMC

• 1 other identifier: ITL-008-INSTAVAC-CRC
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a personalized anti-cancer vaccine protocol which includes an in-situ (in the body) cancer vaccine step which combines killing a single metastatic tumor lesion by use of cryoablation in order to cause the release of tumor-specific markers to the immune system and then injecting bioengineered allogeneic immune cells (AlloStim) into the lesion as an adjuvant in order to modulate the immune response and educate the immune system to kill other tumor cells where ever they reside in the body.

Conditions

Metastatic Colorectal Cancer

Keywords

Cancer Vaccine; AlloStim®; Immunovative; Immunotherapy; Allogeneic Cell Therapy; Cryoablation

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  To assess whether cryoablation combined with AlloStim treatment (arm 1) provides an overall survival (OS) advantage when compared to treatment with cryoablation combined with physician's choice (arm 2).

  from randomization within 30 days of accrual to death for any cause followed for up to 2 years from date of randomization

Secondary Outcomes (2)

• Safety

  168 days from randomization

• Health-Related Quality of Life (HRQoL)

  168 days from randomization

Other Outcomes (2)

• Immunological Response

  168 days from randomization

• Longitudinal changes in tumor burden

  168 days from randomization

Study Arms (2)

AlloStim® treatment

EXPERIMENTAL

The treatment schedule includes: (1) the priming step with two ID AlloStim® injections (Days 0 and 3), an additional two ID injections followed by IV infusion of AlloStim® (Days 7 and 10); (2) the vaccination step with cryoablation of a single metastatic lesion followed by injection of AlloStim® into the ablated tumor and IV infusion of AlloStim® on protocol day 14, followed by IV infusion of AlloStim® on Day 17 (3) the activation step with an IV study drug infusion on Day 21 and (4) the booster step with IV booster infusions of AlloStim® on days 49 and 77. Additional booster infusions can be administered monthly at the discretion of the Investigator.

Biological: AlloStim®; Procedure: cryoablation

Physician's Choice (PC)

OTHER

All subjects will be assigned Physician's Choice (PC) therapy. PC can consist of best supportive care (BSC) or any US-FDA-approved cancer drug (e.g. Cetuximab) administrated as a monotherapy at the manufacturer's recommended dose. The treatment schedule shall be prospectively determined and administered as tolerated.

Procedure: cryoablation; Other: Physician's Choice (PC)

Interventions

AlloStim® BIOLOGICAL

AlloStim® is derived from the blood of normal blood donors and is intentionally mismatched to the recipient. CD4+ T-cells are separated from the blood and differentiated and expanded for 9-days in culture to make an intermediary called T-Stim. AlloStim is made by incubating T-Stim cells for 4h with antibody coated microbeads. The cells with the beads still attached are suspended in infusion media and loaded into syringes. The syringes are shipped refrigerated to the point-of-care.

AlloStim® treatment

cryoablation PROCEDURE

percutaneous ablation of a single metastatic tumor lesion usually in liver. The procedure is conducted under CT or ultrasound image-guidance.

AlloStim® treatment; Physician's Choice (PC)

Physician's Choice (PC) OTHER

Physician's Choice therapy can consist of best supportive care (BSC) or any US-FDA approved cancer drug (e.g. Cetuximab) administrated as a monotherapy at the manufacturer's recommended dose. The treatment schedule shall be prospectively determined and administered as tolerated

Also known as: best supportive care, monotherapy (e.g.Cetuximab)

Physician's Choice (PC)

Eligibility Criteria

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

You may qualify if:

• Adult males and female subjects aged 18 years or older at screening visit
• Pathological diagnosis of colorectal adenocarcinoma
• Metastatic disease with at least one lesion in liver
• Primary can be intact or resected
• Metastatic lesion(s) in liver non-resectable
• Extrahepatic disease acceptable
• KRAS/BRAF mutant disease or KRAS wild type w/previous anti-EGFR treatment
• At least one liver lesion able to be visualized by ultrasound and determined to be safely assessable for percutaneous cryoablation
• Previous treatment failure of at 2 previous lines of active systemic chemotherapy for metastatic disease:
• Previous chemotherapy must have included one line with oxaliplatin (e.g. FOLFOX) and a previous second line with irinotecan (e.g. FOLFIRI) with or without bevacizumab
• If KRAS wild type, at least one anti-EGFR therapy in first or second line
• Treatment failure can be due to disease progression or toxicity
• Disease progression on 2nd line therapy must be documented radiologically and have occurred during or within 30 days following the last administration of 2nd line chemotherapy
• ECOG performance score: 0-1
• Adequate hematological function: Absolute granulocyte count ≥ 1,200/mm3, Platelet count ≥ 100,000/mm3, PT/INR ≤ 1.5 or correctable to \<1.5 at time of interventional procedures, Hemoglobin ≥ 9 g/dL (may be corrected by transfusion)

You may not qualify if:

• Peritoneal carcinomatosis
• Moderate or severe ascites requiring medical intervention
• Prior hepatectomy, ablation or chemoembolization of liver lesion
• Prior pelvic radiotherapy
• Clinical or radiological evidence of brain metastasis/leptomeningeal involvement
• Symptomatic asthma or COPD or any lung condition requiring treatment with steroids
• Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment or oxygen saturation \<92% on room air
• Bevacizumab (Avastin®) treatment within 6 weeks of scheduled cryoablation
• No Regorafenib prior to or during the Study Period
• Anticoagulant medication for concomitant medical condition (unless can be safely discontinued for invasive cryoablation, biopsy and intratumoral injection procedures)
• Prior allogeneic bone marrow/stem cell or solid organ transplant
• Chronic use (\>2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to\>5 mg/day of prednisone) within 30 days of the 1st day of study treatment
• o Topical corticosteroids are permitted
• Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis). Well controlled Type I diabetes allowed.
• Prior experimental therapy

Sponsors & Collaborators

• Mirror Biologics, Inc.: lead

Study Sites (1)

National Cancer Institute of Thailand

Bangkok, Thailand

Location

Related Publications (3)

• Har-Noy M, Zeira M, Weiss L, Fingerut E, Or R, Slavin S. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma. Leuk Res. 2009 Apr;33(4):525-38. doi: 10.1016/j.leukres.2008.08.017. Epub 2008 Oct 1.

  PMID: 18834631 BACKGROUND

• Har-Noy M, Zeira M, Weiss L, Slavin S. Completely mismatched allogeneic CD3/CD28 cross-linked Th1 memory cells elicit anti-leukemia effects in unconditioned hosts without GVHD toxicity. Leuk Res. 2008 Dec;32(12):1903-13. doi: 10.1016/j.leukres.2008.05.007. Epub 2008 Jun 18.

  PMID: 18565579 BACKGROUND

• Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70(6):1186-92. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.

  PMID: 18054441 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cryosurgery

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Wirote Lausoontornsiri, MD

  National Cancer Institute of Thailand

  PRINCIPAL INVESTIGATOR

• Thu Bui, BS

  Mirror Biologics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2012
• First Posted: December 4, 2012
• Study Start: December 1, 2017
• Primary Completion: December 1, 2019
• Study Completion: October 1, 2020
• Last Updated: January 22, 2020

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)