In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol® (Poly-ICLC)
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|ClinicalTrials.gov Identifier: NCT02423863|
Recruitment Status : Recruiting
First Posted : April 22, 2015
Last Update Posted : November 13, 2019
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Head and Neck Cancer Sarcoma Non-Melanoma Skin Cancers||Biological: Hiltonol||Phase 2|
Hide Detailed Description
For purposes of analysis patients enrolled in Stage II of this study will be prospectively identified at initial screening as belonging to statistical Cohorts A, B, or C, which are based on patient status with regard to aPD1/aPDL1 therapy at study entry, (PD, SD, or treatment naïve) per section 11.5. For purposes of this study, patient status is considered to be the primary eligibility variable, although sub analyses will also consider histology and particular checkpoint blocker used when possible. Please see section 12 (Statistical Analysis) for further discussion.
Week 1 Days 1, 3 and 5: Poly-ICLC (Hiltonol®) 1 mg (0. 5 ml) IntraTumoral (priming treatment course).
- Poly-ICLC (Hiltonol®) 1 mg (0.5 ml) IM twice a week with a 48-72 hour interval between the two injections, AND either:
- No additional immunotherapy OR
ONLY ONE of the following Anti-PD1 or anti-PDL-1 regimens will be administered, per manufacturer's dosing and clinical oncologist's discretion as follows: (Not to be Administered on the same day as Poly-ICLC [Hiltonol®])
- Either Nivolumab (Opdivo), OR
- Pembrolizumab (Keytruda), OR
- Atezolizumab (Tecentriq) OR
- Cemiplimab (Libtayo) OR
- Durvalumab (Imfinzi)
NOTE: It is recognized that some patients will have already been on anti-PD-1 or anti-PD-L1 at the time of study entry. Such patients will not have their checkpoint blocker therapy interrupted, but will be started on Poly-ICLC on week one, as above
If well tolerated they continue at full dose of 1 mg IM twice weekly through week 25. Anti-PD-1 or anti-PD-L1 per manufacturers package insert begins on week two and continues through week 25 or beyond per standard of care at physician's discretion. After the end of Poly-ICLC treatment at week 25, aPD1 or aPDL1 can be continued at the discretion of the patient and treating physician, per SOC, independent of this protocol.
At week 26 study subjects will be assessed and response determined using the RECIST 1.1 criteria. This will include measurement of accessible lesions as well as CT scan of the chest, abdomen and pelvis and extremities or neck to assess for response, using RECIST 1.1. MRI of the brain may also be obtained as part of clinical follow of their disease, if clinically indicated as per standard clinical protocol. Study subject's response will be defined as BOR (CR, PR, SD) or PD. If tumors are present and accessible, biopsies of the injected tumor as well as of a non-targeted/non-injected tumor will also be obtained at week 26.
Study subjects with CR, PR, or SD may be offered an additional treatment cycle depending on study subject's health status, costs and/or drug availability. At week 26 a repeat tumor assessment will be performed, an optional biopsy may be performed.
Follow up Period:
After completion of study treatment, study subjects may be contacted by telephone at least twice over 12 months, or longer with patient consent to inquire on their health status (e.g., alive, remission, progressive disease, on new cancer treatment). Study subjects with an initial tumor response but then long-term recurrence during the follow up period may be offered additional cycles of treatment depending on the study subject's health status, costs and/or drug availability.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol® (Poly-ICLC): An Adaptive, Multicenter, Phase II Clinical Study|
|Study Start Date :||March 2015|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: Hiltonol Poly-ICLC
Open labeled, non randomized adaptive 2-stage design protocol. 21 study subjects were enrolled in stage I of the protocol. Up to an additional 60 patients. . Enrolled study subjects will receive Poly-ICLC (Hiltonol®) treatment alone or in combination with anti-PD-1 (Nivolumab, Pembrolizumab or Cemiplimab) or anti-PD-L1 (Atezolizumab or Durvalumab) over 6 months as defined in study treatment described below. MRI or CT imaging will be done per SOC at screening, 3 and 6-month time points.
For purposes of analysis patients enrolled in Stage II of this study will be prospectively identified at initial screening as belonging to statistical Cohorts A, B, or C, which are based on patient status with regard to aPD1/aPDL1 therapy at study entry, (PD, SD, or treatment naïve). For purposes of this study, patient status is considered to be the primary eligibility variable, although sub analyses will also consider histology and particular checkpoint blocker used when possible.
Wk 1 Days 1, 3 and 5: Poly-ICLC (Hiltonol®) 1 mg (0. 5 ml) IntraTumoral (priming treatment course). Weeks 2-25 Poly-ICLC (Hiltonol®) 1 mg (0.5 ml) IM twice a week with a 48-72 hour interval between the two injections, AND either:
No additional immunotherapy OR
ONLY ONE of the Anti-PD1 or anti-PDL-1 regimens will be administered, per manufacturer's dosing and clinical oncologist's discretion as follows: (Not to be Administered on the same day as Poly-ICLC [Hiltonol®]) Either Nivolumab, OR Pembrolizumab, OR Atezolizumab, OR Cemiplimab, OR Durvalumab
- Evaluate safety of intratumoral (IT) plus intramuscular (IM) Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC, Hiltonol®) for treatment of patients with accessible solid tumors, with or with [ Time Frame: Evaluation of response wk 26 ]Wk 26 study subject's response will be defined as BOR (CR, PR, SD) or PD.
- Evaluate therapeutic efficacy assessed by Disease Control (CR, PR, or SD) as defined by the RECIST 1.1 Criteria. [ Time Frame: 6 months ]Week 26 tumor assessment will be performed, an optional biopsy may be performed.
- Determine whether the study regimen of Poly-ICLC will induce an innate and/or an adaptive, specific anti-tumor T cell immune response in the injected tumor lesion and systemically. [ Time Frame: 26 weeks ]Serial blood samples collected at certain time points and processed and used to evaluate humoral and cellular immunity induced by IT and IM polyICLC injections
- Determine the response in injected lesions as defined by change in size at 16 weeks and 26 weeks as assessed by bi-dimensional measurement using RECIST 1.1 criteria. [ Time Frame: 16 weeks and 26 weeks ]In the present protocol, we propose to induce both innate and adaptive cellular immune mechanisms with IT injections of poly-ICLC (Nierkens, den Brock et al. 2008)
- Determine the response in non-injected tumor lesions, both visceral and non-visceral as defined by change in size at 16 weeks and 26 weeks as assessed by bi- dimensional measurement. [ Time Frame: 16 weeks and 26 weeks ]Bi-dimensional measurements will be performed on injected and non-injected lesions at the indicated time points in the study calendar.
- Determine progression free survival at 12, 24, and 36 months in treated study subjects. [ Time Frame: 12, 24 and 36 months ]Up to 5 visible deep measureable lesions will be designated as Target Lesions (index lesions)
- Determine overall survival (OS) in treated study subjects. [ Time Frame: Up to 36 months ]Survival and disease control/progression-free survival (PFS) will be estimated using Kaplan-Meir curves.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423863
|Contact: Andres M Salazar, MD||202 342 email@example.com|
|Contact: Rose Marie Holman, MA||917 885 firstname.lastname@example.org|
|United States, Maryland|
|Chevy Chase RCCA||Recruiting|
|Chevy Chase, Maryland, United States, 20815|
|Contact: Frederick P Smith, MD 301-657-8587 email@example.com|
|Contact: Susan Bendel, RN 301- 657- 8587 firstname.lastname@example.org|
|Dermatologic Surgery Center Washington DC||Recruiting|
|Chevy Chase, Maryland, United States, 20815|
|Contact: Maral K Skelsey, MD 301-652-8081 email@example.com|
|Contact: Xiaophin Bai, MD 301 652 8081 firstname.lastname@example.org|
|Bay Hematology Oncology||Recruiting|
|Easton, Maryland, United States, 2160l|
|Contact: David Smith, MD 410-820-5945 email@example.com|
|Contact: Amy Wright, RN 410 820 5945 ext 4 firstname.lastname@example.org|
|United States, Missouri|
|University of Missouri School of Medicine||Recruiting|
|Columbia, Missouri, United States, 65211-0001|
|Contact: Kevin Staveley-O'Carroll, MD 843-696-8164 email@example.com|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Nina Bhardwaj, MD, PhD 212-824-8427 firstname.lastname@example.org|
|Contact: Denise Rodriguez 212 824 8448 email@example.com|
|Principal Investigator: Nina Bhardwaj, MD, PhD|
|Principal Investigator:||Nina Bhardwaj, MD, PhD||Icahn School of Medicine at Mount Sinai|
|Principal Investigator:||David H Smith, MD||Bay Hematology Oncology|
|Principal Investigator:||Kevin Staveley-O'Carroll, MD||University Missouri|
|Principal Investigator:||Frederick P Smith, MD||Chevy Chase, RCCA|