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Study of AlloStim In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2015 by Immunovative Therapies, Ltd.
Sponsor:
Information provided by (Responsible Party):
Immunovative Therapies, Ltd.
ClinicalTrials.gov Identifier:
NCT01741038
First received: November 29, 2012
Last updated: August 26, 2015
Last verified: August 2015

November 29, 2012
August 26, 2015
January 2016
January 2019   (final data collection date for 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 ] [ Designated as safety issue: No ]
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).
Overall Survival [ Time Frame: the ITT population from randomization within 30 days of accrual to death for any cause followed for up to 2 years from date of randomization ] [ Designated as safety issue: No ]
To assess whether cryoablation combined with AlloStim treatment (arm 1) provides an overall survival (OS) advantage when compared to treatment with cryoablation combined with placebo (arm 2).
Complete list of historical versions of study NCT01741038 on ClinicalTrials.gov Archive Site
  • Safety [ Time Frame: 168 days from randomization ] [ Designated as safety issue: Yes ]
    Safety will be evaluated by physical exam, changes in laboratory values and patient reported symptoms
  • Health-Related Quality of Life (HRQoL) [ Time Frame: 168 days from randomization ] [ Designated as safety issue: No ]
    To assess change in HRQoL between treatment arms
  • Safety [ Time Frame: from randomization ] [ Designated as safety issue: Yes ]
    Safety will be evaluated by physical exam, changes in laboratory values and patient reported symptoms
  • Immunological Response [ Time Frame: from baseline ] [ Designated as safety issue: No ]
    blood samples will be evaluated for immunological response and a determination made as to whether immunological response correlates with survival
  • Immunological Response [ Time Frame: 168 days from randomization ] [ Designated as safety issue: No ]
    blood samples will be evaluated for immunological response and a determination made as to whether immunological response correlates with survival
  • Longitudinal changes in tumor burden [ Time Frame: 168 days from randomization ] [ Designated as safety issue: No ]
    To document the longitudinal changes in tumor burden by Response Evaluation Criteria in Solid Tumors (RECIST) and Immune-Related Response Criteria (irRC)
Not Provided
 
Study of AlloStim In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer
Phase II/III, Randomized, Open Label, Multicenter, Controlled, Two Arm Study Comparing Overall Survival of AlloStim With Cryoablation to a Physician's Choice Third Line Treatment in KRAS and/or BRAF Mutant 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.

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 KRAS-Mutant Metastatic Colorectal Cancer. Subjects are randomized 2:1 into the treatment or control arms.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Colorectal Cancer
  • Biological: AlloStim
    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.
  • Procedure: cryoablation
    percutaneous ablation of a single metastatic tumor lesion usually in liver. The procedure is conducted under CT or ultrasound image-guidance.
  • Drug: Physician's Choice (PC)
    Physician's Choice therapy can consist of any FDA-approved cancer drug administrated as a monotherapy at the manufacturer's recommended dose. The treatment schedule shall be prospectively determined and administered as tolerated
    Other Name: Monotherapy
  • Experimental: AlloStim treatment
    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.
    Interventions:
    • Biological: AlloStim
    • Procedure: cryoablation
  • Active Comparator: Physician's Choice (PC)
    All subjects will be assigned PC therapy (e.g. Cisplatin). PC can consist of any Food and Drug Administration (FDA)-approved cancer drug administrated as a monotherapy at the manufacturer's recommended dose. The treatment schedule shall be prospectively determined and administered as tolerated
    Interventions:
    • Procedure: cryoablation
    • Drug: Physician's Choice (PC)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
450
July 2020
January 2019   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Adult males and female subjects aged 18 years or older at screening visit
  2. Pathological diagnosis of colorectal adenocarcinoma
  3. 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
  4. KRAS/BRAF mutant disease or KRAS wild type w/previous anti-EGFR treatment
  5. At least one liver lesion able to be visualized by ultrasound and determined to be safely assessable for percutaneous cryoablation
  6. 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
  7. ECOG performance score: 0-1
  8. 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)
  9. 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
  10. EKG without clinically relevant abnormalities
  11. Female subjects: Not pregnant or lactating
  12. Subjects with child bearing potential must agree to use adequate contraception
  13. Study specific informed consent in the native language of the subject

Exclusion Criteria:

  1. Peritoneal carcinomatosis
  2. Moderate or severe ascites requiring medical intervention
  3. Prior hepatectomy, ablation or chemoembolization of liver lesion
  4. Prior pelvic radiotherapy
  5. Clinical or radiological evidence of brain metastasis/leptomeningeal involvement
  6. Symptomatic asthma or COPD or any lung condition requiring treatment with steroids
  7. Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment or oxygen saturation <92% on room air
  8. Bevacizumab (Avastin®) treatment within 6 weeks of scheduled cryoablation
  9. No Regorafenib prior to or during the Study Period
  10. Anticoagulant medication for concomitant medical condition (unless can be safely discontinued for invasive cryoablation, biopsy and intratumoral injection procedures)
  11. Prior allogeneic bone marrow/stem cell or solid organ transplant
  12. 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

  13. Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis). Well controlled Type I diabetes allowed.
  14. Prior experimental therapy
  15. History of blood transfusion reactions
  16. Known allergy to bovine products
  17. 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

  18. Cardiac disease of symptomatic nature
  19. History of HIV positivity or AIDS
  20. 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
  21. History of severe hypersensitivity to monoclonal antibody drugs or any contraindication to any of the study drugs
  22. Psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation
Both
18 Years and older
No
Contact: Tali Amir-Azulay, MA 972-2-650-6288 tali@immunovative.co.il
Contact: Thu Bui, BS 1-760-444-9040 thu@immunovative.co.il
Thailand
 
NCT01741038
ITL-008- COCIS-CAVAC
Yes
Immunovative Therapies, Ltd.
Immunovative Therapies, Ltd.
Not Provided
Principal Investigator: Wirote Lausoontornsiri, MD National Cancer Institute of Thailand
Study Director: Tali Amir-Azulay, MA Immunovative Therapies, Ltd.
Immunovative Therapies, Ltd.
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP