A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site

Browse trials for

• Neoplasms, Unknown Primary 104

Study arms

• Experimental
  Molecularly-Guided Therapy

  Participants will be assigned to molecularly-guided therapy based on genomic profile.

  Drug: Alectinib · Drug: Vismodegib · Drug: Ipatasertib · Drug: Olaparib · Drug: Erlotinib · Drug: Bevacizumab · Drug: Vemurafenib · Drug: Cobimetinib · Drug: Trastuzumab Subcutaneous (SC) · Drug: Pertuzumab · Drug: Atezolizumab · Drug: Paclitaxel · Drug: Entrectinib · Drug: Ivosidenib · Drug: Pemigatinib

• Active comparator
  Platinum-Based Chemotherapy

  Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).

  Drug: Trastuzumab Subcutaneous (SC) · Drug: Pertuzumab · Drug: Carboplatin · Drug: Paclitaxel · Drug: Cisplatin · Drug: Gemcitabine

Interventions

• DrugAlectinib

  Alectinib will be administered orally at the label-recommended dose (600 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

• DrugVismodegib

  Vismodegib will be administered orally at the label-recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

• DrugIpatasertib

  Ipatasertib will be administered orally at the label-recommended dose (400 mg) once daily on Days 1-21 of each 28-day Cycle in combination with paclitaxel, and as monotherapy after the final administration of paclitaxel, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

• DrugOlaparib

  Olaparib will be administered orally at the label-recommended dose (400 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

• DrugErlotinib

  Erlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

• DrugBevacizumab

  Bevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

• DrugVemurafenib

  Vemurafenib will be administered orally, 960 mg twice daily, in combination with Cobimetinib, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

• DrugCobimetinib

  Cobimetinib will be administered orally, 60mg once daily, in combination with Vemurafenib, on Days 1-21 of each 28-day Cycle, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

• DrugTrastuzumab Subcutaneous (SC)

  Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

• DrugPertuzumab

  Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)

• DrugAtezolizumab

  Atezolizumab will be administered intravenously at the label-recommended dose (1200 mg), alone or in combination with chemotherapy, every 3 weeks until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

• DrugCarboplatin

  Carboplatin will be administered intravenously at the area under the curve (AUC) dose once every 3 weeks for up to 9 Cycles (Cycle = 21 days) in some combination with the following: Paclitaxel, Gemcitabine, Atezolizumab, Pertuzumab, and Trastuzumab SC.

• DrugPaclitaxel

  Paclitaxel will be administered intravenously, 175 mg/m\^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC

• DrugCisplatin

  Cisplatin will be administered intravenously, 60-75 mg/m\^2, once every three weeks, for up to 9 cycles (Cycle = 21 days) in some combination with the following: Gemcitabine, Paclitaxel, Atezolizumab, Pertuzumab, and Trastuzumab SC.

• DrugGemcitabine

  Gemcitabine will be administered intravenously, 1000 mg/m\^2, twice every three weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Cisplatin, Carboplatin, Atezolizumab, Pertuzumab, and Trastuzumab SC.

• DrugEntrectinib

  Entrectinib will be administered orally at the label-recommended dose (600 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).

• DrugIvosidenib

  Ivosidenib will be administered orally at the label-recommended dose (500mg) once daily across a 28-day treatment cycle until loss of clinical benefit or unacceptable toxicity.

• DrugPemigatinib

  Pemigatinib will be administered orally at the label-recommended dose (13.5mg) once daily across a 21-day treatment cycle until loss of clinical benefit or unacceptable toxicity.

Primary outcomes

1. Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)

   This efficacy objective was to evaluate the efficacy of MGT vs platinum chemotherapy in term of PFS in participants with CUP whose best response to 3 cycles of platinum induction chemotherapy was assessed CR, PR, or SD.

   Time frame: From randomization to the first occurrence of disease progression or death from any cause, until 330 PFS events were observed (approx. 4.3 years for MGT Cat 1 and 3.4 years for Chemotherapy Cat 1).

Secondary outcomes

1. Overall Survival (OS)

   Time frame: From randomization to death from any cause (approx. 4 years)

2. Objective Response Rate (ORR)

   Time frame: Two consecutive occurrences of complete or partial response >/=4 weeks apart (up to approximately 4 months)

3. Duration of Response (DOR)

   Time frame: From the first documentation of a complete response (CR) or partial response (PR) to disease progression or death from any cause, whichever occurs first (up to approximately 4 years)

4. Disease Control Rate (DCR)

   Time frame: From randomization to death from any cause, through the end of study (approximately 4 years)

Baseline characteristics

Publications

• Kramer A, Bochtler T, Pauli C, Shiu KK, Cook N, de Menezes JJ, Pazo-Cid RA, Losa F, Robbrecht DG, Tomasek J, Arslan C, Ozguroglu M, Stahl M, Bigot F, Kim SY, Naito Y, Italiano A, Chalabi N, Duran-Pacheco G, Michaud C, Scarato J, Thomas M, Ross JS, Moch H, Mileshkin L. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet. 2024 Aug 10;404(10452):527-539. doi: 10.1016/S0140-6736(24)00814-6. Epub 2024 Jul 31. PubMed 39096924 ↗

Study documents

• Protocol and statistical analysis plan · Mar 9, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing