A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer

NCT03331562 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: TGen 17-001MISP# 56240
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief Summary

Chemotherapy regimens for pancreatic cancer can now stabilize a patient's cancer and/or place some patients in remission or partial remission. The challenge now is to find options for maintenance therapies that will improve survival and allow continued benefits with minimal toxicities and inconvenience to the patients. This study will determine the effects of one possible maintenance regimen. The study is being conducted to determine the effects that pembrolizumab with or without the addition of paricalcitol may have on pancreatic cancer. Half of the patients will be randomized to receive pembrolizumab + paricalcitol and half to receive pembrolizumab + placebo.

Conditions

Pancreatic Cancer; Pancreas Adenocarcinoma; Advanced Pancreatic Cancer; Metastatic Pancreatic Cancer; Metastatic Pancreatic Adenocarcinoma

Keywords

Pembrolizumab; Paricalcitol; Pancreatic cancer; Metastatic Pancreatic Cancer; Vitamin D Receptor (VDR); Immune Checkpoint Inhibitor; VDR agonist; PD1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression- Free Survival at 6 Months From Initiation of Trial Treatment

  Progression Free Survival (PFS) defined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) survival in the absence of death or progressive disease which is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 21 days.

Secondary Outcomes (4)

• Incidence of Treatment-related Toxicities as Assessed by CTCAE v4.0 From cycle1/Day 1 Through 30 Days After the Last Dose of Trial Treatment.

  initiation of trial treatment cycle 1/day 1 through 30 days after last dose of trial treatment. Each treatment cycle is 21 days.

• Difference in Overall Survival (OS) in Patients Administered the Combination of Paricalcitol Plus Pembrolizumab Versus Pembrolizumab Alone

  From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 24 months ( the end of the study).

• Change in Tumor Mutational Landscape and Transcriptional Programs Using Unbiased Genome-wide Sequencing

  Optional tumor biopsy taken at baseline and at 9 +/- 1 week following initiation of treatment

• Cellular VDR Targets in the Immune Microenvironment With PD1 Blockade

  From baseline, at 9 +/- 1 week following initiation of treatment, at the time of confirmed response, and at the time of trial treatment discontinuation for any reason, up to 24 months ( 35 treatment cycles).

Other Outcomes (5)

• Exploratory: Difference in Disease Progression According to RECIST 1.1 and iRECIST

  tumor assessments performed every 9 +/- 1 week while on treatment, up to 24 months.

• Exploratory: Utility of a Patient Personalized Clinical Benefit (PPCB) Phone Based Application

  From baseline, patients will complete the PPCB App weekly during trial treatment, and at the time of trial treatment discontinuation for any reason, assessed up to 24 months (35 treatment cycles).Each treatment cycle is 21 days.

• Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1

  From baseline, patients will complete the PPCB App weekly during trial treatment, and at the time of trial treatment discontinuation for any reason, assessed up to 24 months (35 treatment cycles). Each treatment cycle is 21 days.

Study Arms (2)

pembrolizumab & paricalcitol

ACTIVE COMPARATOR

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Drug: Pembrolizumab; Drug: paricalcitol

pembrolizumab & placebo

PLACEBO COMPARATOR

pembrolizumab 200 mg IV q 3 weeks \& placebo- normal saline IV 3 xs per week

Drug: Pembrolizumab; Drug: placebo

Interventions

Pembrolizumab DRUG

pembrolizumab solution for infusion

Also known as: Keytruda

pembrolizumab & paricalcitol; pembrolizumab & placebo

paricalcitol DRUG

Paricalcitol solution for injection

Also known as: Zemplar

pembrolizumab & paricalcitol

placebo DRUG

normal saline solution for injection

Also known as: placebo for paricalcitol

pembrolizumab & placebo

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Histologically or cytologically confirmed pancreatic adenocarcinoma with metastasis, who had obtained a best response of at least stable disease (SD) or a partial response (PR) for a period of 2 months with no further shrinkage of ≥ 30% on scan on their first line of chemotherapy for their advanced metastatic disease. Note: Patients that have had prior chemotherapy as adjuvant or neoadjuvant therapy are permitted.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• Able to submit an archival tumor specimen (primary or metastatic site) and a discussion is documented with trial investigator at screening that patient will consider providing tissue from a newly obtained core or excisional biopsy of a tumor lesion at baseline and a second biopsy 9 weeks after starting trial treatment, unless tumor is considered inaccessible or biopsy is otherwise considered not in the patients best interest. Participation in this trial is not contingent on patient consenting to optional tumor biopsies.
• Demonstrate adequate organ function as defined in protocol, AND serum corrected calcium value must be ≤ Institutional Upper Limit of Normal (ULN) and ≥ 8.0 mg/dL, and phosphorus levels must be ≤ Institutional ULN and ≥ 2.5 mg/dL.
• Female participants of childbearing potential should have a negative serum pregnancy test within 24 hours prior to receiving first dose of trial medication.
• A female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in protocol
• A WOCBP who agrees to follow the contraceptive guidance in protocol during the treatment period and for at least 120 days after the last dose of trial treatment.
• Male participants must agree to use a contraception as detailed in protocol during the treatment period and for at least 120 days after the last dose of trial treatment and refrain from donating sperm during this period.

You may not qualify if:

• Is currently participating and receiving trial therapy or has participated in a trial of an investigational agent and received trial therapy or used an investigational device within 4 weeks of the first dose of trial treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
• Has a known history of active TB (Mycobacterium tuberculosis).
• Hypersensitivity to pembrolizumab or paricalcitol or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to Cycle 1/Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle1/ Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent(s).
• Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the trial.
• Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• Translational Genomics Research Institute: lead
• Stand Up To Cancer: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Atlantic Medical Group-Oncology Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

Baylor University Medical Center Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Froedtert Hospital and Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Chung V, Alistar A, Becerra C, Kasi A, Borazanci E, Jameson GS, Roe DJ, Wertheim BC, Cridebring D, Truitt M, Downes M, Barrett MT, Korn R, Lee K, Han H, Evans R, Von Hoff DD. Pembrolizumab +/- paricalcitol in metastatic pancreatic cancer postmaximal cytoreduction. Oncologist. 2025 Jan 17;30(1):oyae323. doi: 10.1093/oncolo/oyae323.

  PMID: 39846984 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

pembrolizumab; paricalcitol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Limitations and Caveats

Due to lack of grant funding, the other exploratory objectives to assess the changes in tumor and/or tissue texture on imaging, and to monitor and compare gut microbial communities in both arms, have not yet been able to be accomplished. The Investigators are looking for some way to fund the exploratory objectives in the future.

Results Point of Contact

• Title: Derek Cridebring, PhD. Director, Molecular Medicine Division
• Organization: Translational Genomics Research Institute (TGen) An Affiliate of City of Hope

dcridebring@tgen.org

6023438629

Study Officials

• Daniel D Von Hoff, MD, FACS

  Translational Genomics Research Institute (TGen) An Affiliate of City of Hope

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a double-blind, randomized, placebo-controlled phase II trial with the identity of the treatment unknown to the patients, investigators, and the Sponsor.

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: November 6, 2017
• Study Start: December 27, 2017
• Primary Completion: June 29, 2020
• Study Completion: July 10, 2020
• Last Updated: December 27, 2022
• Results First Posted: December 27, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)