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Metastatic Colorectal CancerPhase 2/3NCT01741038

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

A Phase 2/3 study testing AlloStim®, cryoablation and Physician's Choice (PC) in people with Metastatic Colorectal Cancer, run by Mirror Biologics, Inc. at 1 site in Thailand.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
AlloStim®, cryoablation and Physician's Choice (PC)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteThailand
Study dates
Dec 2017to Oct 2020
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 20Show fewer
  • 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)
  • Adequate Organ Function: Creatinine ≤ 1.5 mg/dL, Total bilirubin ≤ 1.5 times ULN, Alkaline phosphatase ≤ 2.5 times ULN, AST or SGOT ≤ 2.5 times ULN, ALT or SGPT≤2.5 times ULN
  • EKG without clinically relevant abnormalities
  • Female subjects: Not pregnant or lactating
  • Subjects with child bearing potential must agree to use adequate contraception
  • Study specific informed consent in the native language of the subject

Who cannot join

  • 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
Show all 24Show fewer
  • 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
  • History of blood transfusion reactions
  • Known allergy to bovine products
  • Progressive viral or bacterial infection
  • o All infections must be resolved and the patient must remain afebrile for seven days without antibiotics prior to being placed on study
  • Cardiac disease of symptomatic nature
  • History of HIV positivity or AIDS
  • Concurrent medication known to interfere with platelet function or coagulation (e.g., aspirin, ibuprofen, clopidogrel, or warfarin) unless such medications can be discontinued for an appropriate time period based on the drug half-life and known activity (e.g., aspirin for 7 days) prior to cryoablation procedure
  • History of severe hypersensitivity to monoclonal antibody drugs or any contraindication to any of the study drugs
  • Psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation

Trial locations and contacts

1 site in 1 country.

Thailand1 site

  • National Cancer Institute of Thailand

    Bangkok

Other trials in Thailand

About this study

Official title: A Phase II/III, Randomized, Open Label, Controlled, Two Arm Study Comparing Overall Survival of AlloStim® Combined With Cryoablation to a Physician's Choice Combined With Cryoablation in 3rd Line Treatment for Metastatic Colorectal Cancer

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.

Read the detailed description

Colorectal cancer (CRC) ranks as the third most common cancer worldwide. Metastasis is the main reason of death in CRC patients. The current drugs used to treat colorectal cancer provide important treatment options for patients, their limitations including drug resistance, poor efficacy and severe side effects. Development of new therapeutic strategies for KRAS mutant as well as BRAF mutant tumors are therefore highly needed in order to offer a new category of drug (immunotherapy). This study targets the population of mCRC patients that have progressed after two lines of chemotherapy and are not eligible for targeted therapies due to a mutation in KRAS or BRAF.

This is a Phase II/III, randomized, open-label, multicenter, controlled, two arm study designed to determine the efficacy in terms of OS and the safety of the InSituVax (AlloStim+ Cryoablation) personalized in-situ anti-cancer vaccine protocol (Treatment Arm) compared with Physician's Choice (PC) of Treatment + Cryoablation (Control Arm) in Metastatic Colorectal Cancer. Subjects are randomized 2:1 into the treatment or control arms.

Being tested
AlloStim®, cryoablation, Physician's Choice (PC)
Keywords
Cancer Vaccine, AlloStim®, Immunovative, Immunotherapy, Allogeneic Cell Therapy, Cryoablation
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • cryoablationProcedure or surgery

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

  • Physician's Choice (PC)Other

    Also called best supportive care, monotherapy (e.g.Cetuximab)

    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

Study groups in NCT01741038
Study groupRoleWhat they receive
AlloStim® treatmentExperimentalThe 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.
Receives: Biological: AlloStim®; Procedure: cryoablation
Physician's Choice (PC)OtherAll 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.
Receives: Procedure: cryoablation; Other: Physician's Choice (PC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 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)

  1. Safety

    Safety will be evaluated by physical exam, changes in laboratory values and patient reported symptoms

    Measured: 168 days from randomization

  2. Health-Related Quality of Life (HRQoL)

    To assess change in HRQoL between treatment arms

    Measured: 168 days from randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2012 (estimated)
  2. Study startDec 2017 (estimated)
  3. Primary completionDec 2019 (estimated)
  4. Study completionOct 2020 (estimated)

Why it stopped: moved study to USA

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01741038
Sponsor's protocol ID
ITL-008-INSTAVAC-CRC
Status last verified
Aug 2016
First submitted
29 Nov 2012
Last updated
22 Jan 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 18834631

  • 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.

    PubMed 18565579

  • 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.

    PubMed 18054441

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing AlloStim®, cryoablation and Physician's Choice (PC) in people with Metastatic Colorectal Cancer, run by Mirror Biologics, Inc. at 1 site in Thailand.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: from randomization within 30 days of accrual to death for any cause followed for up to 2 years from date of randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01741038, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020.

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