RADVAX: A Stratified Phase I Trial of Pembrolizumab With Hypofractionated Radiotherapy in Patients With Advanced and Metastatic Cancers

NCT02303990 | Completed Phase 1 Results DMC

• 1 other identifier: UPCC 40914
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I clinical trial of hypofractionated radiotherapy to an isolated index lesion in combination with the PD-1 inhibitor, Pembrolizumab in patients with metastatic cancers who have failed anti-PD-1 therapy (melanoma and NSCLC) and patients with metastatic cancers who have have progressed after at least one regimen of systemic therapy (breast, pancreas, and other).

Conditions

Metastatic Cancers

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  2 years

Study Arms (1)

Single arm

EXPERIMENTAL

Hypofractionated RT and Pembro

Drug: Pembrolizumab; Radiation: Radiotherapy

Interventions

Pembrolizumab DRUG

Single arm

Radiotherapy RADIATION

Single arm

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/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• Histologically confirmed diagnosis of cancer as per the cohort specifications
• Stage IV cancer by AJCC staging criteria (except for pancreatic cancer cohort)
• Locally advanced or metastatic pancreatic cancer for the pancreatic cancer cohort
• Progression of disease while on anti-PD-1 or anti-PD-L1 therapy for melanoma and NSCLC patients. For this group, patients must met the following criteria:
• Received at least 2 doses of an anti-PD1 or anti-PD-L1 therapy
• Had progressive disease documented radiologically by RECIST v1.1 criteria.
• Progression or refractory disease to at least one regimen of therapy for metastatic disease in the breast and pancreatic cancer cohorts
• Presence of an index lesion \> 1 cm amenable to hypofractionated radiotherapy
• Patients who have metastatic cancer must have at least one lesion that is outside the radiation field that measures greater than one cm that can be followed by RECIST 1.1. This lesion, if it is close to the radiated lesion, must receive no more than 10% of the dose prescribed to the target lesion.
• Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Ability to tolerate hypofractionated radiation therapy (e.g. lie flat and hold position)
• Demonstrate adequate organ function , all screening labs should be performed within 14 days of treatment initiation.

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of 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. Systemic steroids administered specifically as a premedication for chemotherapy infusion or radiotherapy are allowed.
• Has had a prior monoclonal antibody within 4 weeks prior to study 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 study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• A history of prior radiotherapy that precludes delivery of hypofractionated radiotherapy
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects 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.
• Has an active automimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, non-infectious 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 subject's participation for the full duration of the trial, or is not in the best interest of the subject 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.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Maity A, Mick R, Huang AC, George SM, Farwell MD, Lukens JN, Berman AT, Mitchell TC, Bauml J, Schuchter LM, O'Hara M, Lin LL, Demichele A, Christodouleas JP, Haas NB, Patsch DM, Hahn SM, Minn AJ, Wherry EJ, Vonderheide RH. A phase I trial of pembrolizumab with hypofractionated radiotherapy in patients with metastatic solid tumours. Br J Cancer. 2018 Nov;119(10):1200-1207. doi: 10.1038/s41416-018-0281-9. Epub 2018 Oct 15.

  PMID: 30318516 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Dr. Amit Maity
• Organization: University of Pennsylvania

maity@uphs.upenn.edu

215) 662-3759

Study Officials

• Amit Maity, MD, PhD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2014
• First Posted: December 1, 2014
• Study Start: January 8, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 31, 2019
• Last Updated: May 12, 2021
• Results First Posted: April 22, 2021

Record last verified: 2021-04

Locations

US (1)