AzTrials
AzTrials

Advanced Ovarian CancerPhase 1ACTIVATENCT03158935

The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial

A Phase 1 study testing Cyclophosphamide, Fludarabine and Pembrolizumab in people with Advanced Ovarian Cancer and Malignant Melanoma, run by University Health Network, Toronto at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a phase 1b study for patients with metastatic (cancer has spread to various parts of the body) melanoma and ovarian cancer. The main purpose is to examine the safety and efficacy of administering pembrolizumab after receiving chemotherapy, tumor-infiltrating lymphocytes (TIL) and low dose interleukin 2 (IL-2). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Ovarian Cancer, Malignant Melanoma
What is being tested?
Cyclophosphamide, Fludarabine and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteCanada
Study dates
7 Jul 2017to 4 Aug 2020
Phase
Phase 1
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

None listed.

Who cannot join

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used 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.
  • Has a known history of active, untreated TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) 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 within 28 days prior to study Day 1, or targeted small molecule therapy or radiation therapy within 14 days prior to study Day 1. Patients who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
Show all 26Show fewer
  • 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, superficial bladder cancer, and in situ cervical cancer that has undergone potentially curative therapy.
  • 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of 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 6 months after last dose of cyclophosphamide or fludarabine or 120 days after the last dose of pembrolizumab.
  • Has a known history of Human Immunodeficiency Virus (HIV) (e.g. HIV 1/2 antibody positive) or Human T-Cell Lymphotropic Virus (HTLV).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Untreated syphilis.
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Subjects with ongoing prior use of systemic steroid therapy within 4 weeks before the TILs infusion will be excluded. Use of topical, intranasal and inhaled corticosteroids, or systemic corticosteroids at physiologic doses are allowed.
  • Cohort 1 and 2 Post-TIL (pembrolizumab) inclusion criteria:
  • Previously met applicable inclusion and exclusion criteria.
  • Initiation of pembrolizumab therapy must occur more than 21 days after the last dose of fludarabine.
  • Resolution of TIL protocol related adverse events to grade 2 or less. Otherwise, patients may proceed with pembrolizumab therapy if the treating investigator, after discussion with the Sponsor, determines that residual TIL therapy related adverse events are not clinically significant.
  • Cohort 1 and 2 Post-TIL (pembrolizumab) exclusion criteria:
  • Has an active infection requiring systemic therapy. (Prophylactic antibiotics and antiviral agents are allowed.)
  • Has developed a condition or requires a therapy 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.
  • Development of a condition that, in the opinion of the investigator, would be a contraindication for initiating pembrolizumab therapy.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Phase Ib Trial of Pembrolizumab Administered in Combination With or Following Adoptive Cell Therapy- A Multiple Cohort Study; The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial

This is a phase 1b study for patients with metastatic (cancer has spread to various parts of the body) melanoma and ovarian cancer. The main purpose is to examine the safety and efficacy of administering pembrolizumab after receiving chemotherapy, tumor-infiltrating lymphocytes (TIL) and low dose interleukin 2 (IL-2).

Patients will first receive either cyclophosphamide, or cyclophosphamide and fludarabine. These are chemotherapy agents that prepare the body to receive TILs.

Read more

Patients are then infused with autologous TILs, a type of white blood cell that recognizes tumor cells and enters them, thereby causing tumor cells to break down.

Following TILs infusion, patients will receive low-dose IL-2 therapy. This is a type of protein that is intended to activate and stimulate the growth of cells in the patient's immune system.

If the patient meets the required criteria, they will be given pembrolizumab, a monoclonal antibody (drug made up of cloned immune cells) that is designed to block a protein called programed cell death ligand 1 (PD-L1) which will allow the body's immune system to kill the cancer cells.

Read the detailed description

This study will involve treatment with chemotherapy, TILs, IL-2, pembrolizumab, tests and procedures done for safety, and the collection of archival tumor tissue, fresh tumor biopsies, and blood samples for biomarker research.

Being tested
Cyclophosphamide, Fludarabine, Pembrolizumab, Tumor-Infiltrating Lymphocytes (TILs), Interleukin-2 (IL-2)
Keywords
adoptive cell therapy, melanoma, ovarian, cyclophosphamide, fludarabine, tumor-infiltrating lymphocytes (TILs), pembrolizumab, interleukin-2, anti-PD-1, immune checkpoint
Medical subject headings
Melanoma

What participants receive

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

  • CyclophosphamideDrug

    Also called Cytoxan, Procytox

    Cohort 1: i.v., 60mg/kg per day for 2 days Cohort 2: i.v., 30mg/kg per day for 2 days

  • FludarabineDrug

    Also called Fludara

    Cohort 1: i.v., 25mg/m2 per day for 5 days

  • PembrolizumabProcedure or surgery

    Also called Keytruda, MK-3475

    Cohort 1 and 2: i.v., 200mg every 3 weeks

  • Tumor-Infiltrating Lymphocytes (TILs)Biological

    Cohort 1 and 2: i.v., 1x10^10 - 1.6x10^11 cells

  • Interleukin-2 (IL-2)Biological

    Also called Aldesleukin, Proleukin, Recombinant Human Interleukin 2

    Cohort 1 and 2: i.v., 125,000 IU/kg subcutaneous per day

Study groups in NCT03158935
Study groupRoleWhat they receive
Advanced metastatic melanoma (Cohort 1)ExperimentalCyclophosphamide and fludarabine followed by Tumor-Infiltrating Lymphocytes (TILs), Interleukin-2 (IL-2), and pembrolizumab
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Pembrolizumab; Biological: Tumor-Infiltrating Lymphocytes (TILs); Biological: Interleukin-2 (IL-2)
Advanced ovarian cancer (Cohort 2):ExperimentalCyclophosphamide followed by Tumor-Infiltrating Lymphocytes (TILs), Interleukin-2 (IL-2), and pembrolizumab
Receives: Drug: Cyclophosphamide; Procedure: Pembrolizumab; Biological: Tumor-Infiltrating Lymphocytes (TILs); Biological: Interleukin-2 (IL-2)

What is being measured

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

  1. Monitoring of serious adverse events to determine the safety of initiating pembrolizumab following lymphodepleting chemotherapy, TIL administration, and low dose IL-2 injections within 35 days of TIL infusion.

    Toxicities will be monitored on an ongoing basis. Severe adverse events will be reviewed for attribution to the study drug and whether they resolve to an acceptable grade within 35 days of TIL infusion. This information will be used to determine if the patient will go on to receive pembrolizumab. The regimen will be deemed feasible if at least 80% of patients enrolled go on to receive pembrolizumab.

    Measured: 2 years

Secondary outcomes (3)

  1. Overall Response Rate

    To evaluate the response rate of pembrolizumab following or in combination with ACT using measurable disease by RECIST v1.1.

    Measured: 2 years

  2. Overall and Progression Free Survival

    To evaluate the survival outcomes of overall and progression free survival per tumour type

    Measured: 2 years

  3. Safety profile of pembrolizumab therapy given after or in combination with ACT in patients with advanced melanoma and ovarian cancer using CTCAE v4.0

    Events that are both unrelated and related to treatment will be captured using CTCAE v4.0. The total number of episodes for each event will be reported, as well as the severity and attribution to study therapy.

    Measured: 2 years

Timeline

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

  1. First posted18 May 2017
  2. Study start7 Jul 2017
  3. Primary completion4 Aug 2020
  4. Study completion4 Aug 2020

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03158935
Sponsor's protocol ID
ACTIVATE
Acronym
ACTIVATE
Status last verified
Aug 2020
First submitted
9 May 2017
Last updated
14 Aug 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Fludarabine and Pembrolizumab in people with Advanced Ovarian Cancer and Malignant Melanoma, run by University Health Network, Toronto at 1 site in Canada.

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 0 inclusion and 26 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: finished, as of the sponsor's last update on 14 Aug 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 Canada. 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 phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Monitoring of serious adverse events to determine the safety of initiating pembrolizumab following lymphodepleting chemotherapy, TIL administration, and low dose IL-2 injections within 35 days of TIL infusion. (time frame: 2 years). 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 NCT03158935.

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 14 Aug 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in